Journal articles on the topic 'BIN discordance'

Abstract The definition of sarcopenia continues to evolve, creating difficulty in determining the diagnosis and prognosis of the newly classified disease. The most common definitions include a combination of (a) muscle mass [measured using proxies of muscle mass—appendicular lean soft tissue via dual-energy X-ray absorptiometry (DXA) or bioelectrical impedance analysis (BIA)]; (b) muscle strength (often measured using hand grip strength); and (c) physical function (measured using gait speed). However, each consensus definition uses different combinations of muscle mass, strength and physical function to operationalize the definition of sarcopenia. Additionally, each group recommends various measures and cutoff points to capture these outcomes. For example, the European Working Group on Sarcopenia in Older People (EWGSOP) recommends appendicular lean mass for muscle mass, grip strength or chair stand for muscle strength, and gait speed, short performance physical battery, timed up and go, or 400-m walk test for physical function. The Asian Working Group for Sarcopenia (AWGS) uses DXA or BIA, grip strength and 6-m gait speed for muscle, strength and function, respectively. Using different consensus group definitions results in differences in the prevalence of sarcopenia, and there would be, at best, a modest agreement between the various definitions, which would be attributed to the lack of criterion standards.

La riduzione in schiavitù per debiti di Ateniesi prima della seisachtheia di Solone è ben documentata. Le principali fonti sono Solone (fr. 4 e 36 W), Aristotele ([Arist.] Ath. Pol. 2.2.) e Plutarco (Sol. 13.2-3). Tuttavia vi sono discordanze tra le fonti e, di conseguenza, molti dubbi riguardo a questo tema. La legge di Solone sull’amnistia (Plut. Sol. 19.4) faceva probabilmente parte delle misure miranti a eliminare la schiavitù per debiti. Lo scopo che qui si persegue è di fare più luce sulla questione analizzando il significato di atimos e di agogimos in relazione alla situazione dei debitori del tempo.

There is a huge waiting list for recipient of heart for people in need of, yet the pool of donors are limited to less than 10% of all brain death cases coming out of road accidents. NHSA reports 2700 Transplants were harvested out of 55000 road accident brain deaths in 2014. A country (China) expects a record number of transplant this year mainly harvested from executed prisoners (world number one in execution followed by IRAN), despite a new ban applied this year (The south China Morning Post). So one of the most exciting donor pool which also is very close genetically to Human being is Baboon, in which we will try to reignite interest in research and development for farming and harvesting their organs for use in people in need of Cardiac Transplant.

This article addresses the factors leading to Al Qaeda’s continued fragmentation and the collapse of its efforts to create a jihadi state in the Levant. It does so in two parts. First, we look at Al Qaeda’s development of its far enemy strategy that deviated from past jihadi warfare strategies. Second, we examine Al Qaeda’s dysfunctional response to the Arab Spring. The protests untethering of Mideast states and its inflammation of sectarian tensions accelerated Al Qaeda’s transformation into a fractured network committed to localized (increasingly sectarian) insurgencies. After bin Laden’s 2011 killing, Zawahiri in September 2013 released his General Guidelines for the Work of Jihad to tie Al Qaeda’s branches localized insurgencies to a wider struggle against the Zionist-Crusader dominated world order.1 He failed to do so. Upon exploring jihadism’s splintering into three discordant factions represented by Al Qaeda’s far enemy focus, ISIS sectarianism and Hayat Tahrir al-Sham’s (HTS) localized insurgencies, this article concludes that this development has led to an ineffective but dangerously resilient global jihadi movement. Key words: Jihadism, extremism, sectarianism, insurgency Received: 2022-12-17 Revised: 2023-01-15

Abstract Genome duplication with hybridization, or allopolyploidization, occurs in animals, fungi and plants, and is especially common in crop plants. There is an increasing interest in the study of allopolyploids because of advances in polyploid genome assembly; however, the high level of sequence similarity in duplicated gene copies (homeologs) poses many challenges. Here we compared standard RNA-seq expression quantification approaches used currently for diploid species against subgenome-classification approaches which maps reads to each subgenome separately. We examined mapping error using our previous and new RNA-seq data in which a subgenome is experimentally added (synthetic allotetraploid Arabidopsis kamchatica) or reduced (allohexaploid wheat Triticum aestivum versus extracted allotetraploid) as ground truth. The error rates in the two species were very similar. The standard approaches showed higher error rates (>10% using pseudo-alignment with Kallisto) while subgenome-classification approaches showed much lower error rates (<1% using EAGLE-RC, <2% using HomeoRoq). Although downstream analysis may partly mitigate mapping errors, the difference in methods was substantial in hexaploid wheat, where Kallisto appeared to have systematic differences relative to other methods. Only approximately half of the differentially expressed homeologs detected using Kallisto overlapped with those by any other method in wheat. In general, disagreement in low-expression genes was responsible for most of the discordance between methods, which is consistent with known biases in Kallisto. We also observed that there exist uncertainties in genome sequences and annotation which can affect each method differently. Overall, subgenome-classification approaches tend to perform better than standard approaches with EAGLE-RC having the highest precision.

In this study we compared DNA barcode-suggested species boundaries with morphology-based species identifications in the amphipod fauna of the southern European Atlantic coast. DNA sequences of the cytochrome c oxidase subunit I barcode region (COI-5P) were generated for 43 morphospecies (178 specimens) collected along the Portuguese coast which, together with publicly available COI-5P sequences, produced a final dataset comprising 68 morphospecies and 295 sequences. Seventy-five BINs (Barcode Index Numbers) were assigned to these morphospecies, of which 48 were concordant (i.e., 1 BIN = 1 species), 8 were taxonomically discordant, and 19 were singletons. Twelve species had matching sequences (<2% distance) with conspecifics from distant locations (e.g., North Sea). Seven morphospecies were assigned to multiple, and highly divergent, BINs, including specimens of Corophium multisetosum (18% divergence) and Dexamine spiniventris (16% divergence), which originated from sampling locations on the west coast of Portugal (only about 36 and 250 km apart, respectively). We also found deep divergence (4%–22%) among specimens of seven species from Portugal compared to those from the North Sea and Italy. The detection of evolutionarily meaningful divergence among populations of several amphipod species from southern Europe reinforces the need for a comprehensive re-assessment of the diversity of this faunal group.

Összefoglaló. Bevezetés: A HbA1c integrált retrospektív mutatója az elmúlt időszak vércukrának, rendszeres vizsgálata a cukorbetegek anyagcserekontrolljának megítélésében elengedhetetlen. Helyes értékelése azonban nem egyszerű, mert a HbA1c és a vércukor közötti összefüggés nem lineáris. A mérést közvetlenül megelőző hyperglykaemiás epizódok hatása a HbA1c szintjére nagyobb, mint azoké, amelyek régebben történtek. A jelenségre a glikáció biokinetikus modellje ad magyarázatot. Célkitűzés: A mért és a biokinetikus modell alapján számított HbA1c közötti egyezés, illetve diszkordancia vizsgálata. Módszer: A vizsgálatokat 157, 1-es és 2-es típusú cukorbeteg 1793, laboratóriumban mért éhomi vércukor- és 511 HbA1c-adatából végeztük. A különbséget a glikációs index segítségével számítottuk, amely a mért és a számított HbA1c-érték aránya. Eredmények: Egyezést mindössze a vizsgált betegek kevesebb mint egyötödödében találtunk, 60%-ban az index értéke alacsony (<0,95) és 21%-ban magas (>1,05) volt. Az adatok részletes analízise szerint jó anyagcserekontroll esetében gyakoribb a vártnál magasabb, mért HbA1c-érték, mint a biokinetikus egyenlet által számítotté, és rosszabb kontroll (magasabb átlagos vércukor) esetében ez fordítva van. Egyezés esetén a regressziós egyenlet együtthatói gyakorlatilag azonosak a modell alapján számított értékekkel. Következtetés: Vizsgálataink felvetik azt a lehetőséget, hogy a biokinetikus modell magyarázatot adhat a vércukor és a HbA1c közötti diszkordanciára. Orv Hetil. 2021; 162(41): 1652–1657. Summary. Introduction: HbA1c is an integrated retrospective marker of previous blood glucose concentrations and its regular measurement is indispensable in the assessment of glycaemic compensation of diabetic patients. However, its proper interpretation is not simple becasuse the relationship between HbA1c and average glycemia is not a linear one. Hyperglycemic episodes occuring immediately before the measurement have greater impact on the HbA1c level as compared with those taking place earlier. Objective: Assessment of concordance and discordance between measured and according to the biokinetic model calculated values of HbA1c. Method: The calculations were made from averages of 1793 fasting blood glucose and 511 HbA1c of 157, type 1 and 2 diabetic patients. The glycation index is the quotient between measured and calculated HbA1c. Results: Agreement was found in less than one fifth of the 157 patients; in 60% the value of glycation was low (<0.95) and in 21% high (>1.05). Analysis of the glycation index according to the level of glycemic compensation revealed that in patients with good compensation, the measured HbA1c value was more often higher than the expected and in patients with unsatisfactory compensation the opposite was true. Conclusion: These results raise the possibility that the discordance between average glycemia and measured HbA1c can be explained by the biokinetic model. Orv Hetil. 2021; 162(41): 1652–1657.

Abstract Background: Multi-modal analysis is crucial for deeper understanding of disease subtypes and more meaningful patient selection. We developed a flexible Knowledge Graph (KG) framework that enables deep multi-omic analysis. It can be used to uncover the interrelationships between the layers of data in a population to inform patient selection or biomarker discovery. We present an application of our framework to non-small cell lung cancer (NSCLC) to identify and separate communities of patients based on their survival and identify the associated biomarkers. We identified potentially mislabeled patients that do not share all the characteristics of the cancer subtype to which they are assigned: either lung adenocarcinoma (LUAD) or lung squamous cell carcinoma (LUSC). Crucially, the community-based biomarkers for poor or long survivors were validated on the whole population. Methods: Our KG framework was leveraged by applying supervised community detection to NSCLC data from TCGA, specifically RNA expression and DNA methylation, with overall survival (OS) as the endpoint (n=999 subjects). Biomarkers associated to each community were ranked based on their prevalence inside against their prevalence outside the community. Results: We obtained 3 communities (391 + 229 + 379 patients) that are all significantly separated by their OS (p<0.05). While KG-derived communities largely overlapped with histology-labelled LUAD or LUSC (concordant LUAD (n=330)/concordant LUSC (n=342)), a small number of patients did not (discordant LUAD (n=37)/discordant LUSC (n=61)). Discordant LUAD patients had significantly lower OS than concordant LUAD (p=0.0198), despite being both labeled as LUAD. Many of the discordant LUSC lacked the 3q26 amplification commonly seen in LUSC and other squamous cell carcinomas. The results from our KG framework highlight its increased sensitivity in relation to existing tools (Cline, Sci Rep 3, 2652 (2013)) as we identified a discordant LUAD group in addition to a discordant LUSC group. Moreover, our tool can select the biomarkers most prevalent in each community, and these significantly separated long from poor survivors on the whole population (p=3.53e-5). Some of these KG-identified biomarkers are known regulators of progression and survival in NSCLC, whereas others are still not extensively studied. This highlights another advantage of our approach in prospective target discovery. Conclusions: Our KG framework allowed the observation of potential misclassifications of tumor subtypes in NSCLC (TCGA). This approach is a proof-of-concept of the value KGs have in identifying signals in muti-omic data that may improve patient stratification and uncover associated biomarker signatures. Our flexible end-to-end framework can take any type of ‘omic data and can be applied to any tumor type for such findings, which represents an alternative to pre-defined KG architectures with defined relationships. Citation Format: Miguel Goncalves, Jake Cohen-Setton, Ioannis Kagiampakis, Ben Sidders, Krishna Bulusu. Multi-modal knowledge graphs enhance patient stratification & biomarker discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4888.

Abstract After more than seventy years, when Kahlil Gibran’s 1923 masterpiece The Prophet had circulated freely in Egypt, censorship authorities banned the book in 1999 and 2011. This article explores the sociopolitical context surrounding the censorship of The Prophet and its Arabic translations, with a particular focus on the power play between censors and different agents and the strategies employed by the latter to revoke the ban on the book. The extent and intensity of power intervention speak to this case study’s significance. Qualitative analysis of English and Arabic press material is utilized to gain insights into the censors’ reports and the responses of different sociopolitical agents. This is paired with compiling and analyzing a dataset of bibliographical information on the editions of The Prophet’s Arabic translations published in Egypt between 1999 and 2022. The findings point to a decentralized system of censorship exercised by several ministries and religious institutions with competing interests. It is argued that the survival of The Prophet in the face of multiple bans can be attributed to shifting sociopolitical conditions, discordant politics of powerful agents, and international pressure.

Se estima los gradientes paleogeotérmicos a partir de las relaciones reflectancia de vitrinita-profundidad (-z) para sedimentos del Mioceno Tardío en las áreas de Tanakura y Hirono del noreste de Japón. Ambas áreas se han situado en la región ante arco desde hace 15 Ma y no han sido afectadas por magmatismo. Estos sedimentos debieron haber sufrido disturbios térmicos locales limitados, y por ello resultan adecuados para estudiar las condiciones paleogeotérmicas a una escala regional. El levantamiento que se llevo a cabo en la región, entre el Mioceno Tardío y el Plioceno Temprano dio como resultado una discordancia angular entre las rocas miocénicas y pliocénicas y causó el enfriamiento de los sedimentos del Mioceno, lo que pudo haber retardado y detenido en forma efectiva el proceso de carbonización. Las relaciones -z de los sedimentos, por lo tanto, revelan el gradiente geotérmico entre la depositación y el destechamiento. El gradiente paleogeotérmico estimado es de 64±11° en el subsuelo fue mayor en el Mioceno Tardío que en el presente, debajo del ante-arco. Un enfriamiento de escala regional a través del arco parece haber tenido lugar a partir del Plioceno y durante todo el Cuaternario, tal como lo sugiere la firma geoquímica de las rocas volcánicas del frente volcánico (Ban et al., 1992). Un retroceso hacia el occidente del frente volcánico (Ohguchi et al., 1989) es consistente también con el enfriamiento regional.

In The Muses' Concord, James H. Jensen observes that rhetorical theory and practice ground all the arts of the Renaissance era (47). This connection is evident in the discourse of rhetorical and dance performance shared between Classical rhetoric treatises and Renaissance dance manuals, which leads one to understand both arts equally as forms of ordered and measured language. The recognition and perspectives of dance as a form of rhetoric contribute much to our understanding of the culture's awareness and economy of nonverbal communication. The shared elements of rhetoric and dance can be observed in the sheep-shearing festival scene of The Winter's Tale (4.4). A rhetorical reading of this scene conveys the rhetorical quality of dance, as well as its dramaturgical function. Framing this reading is a cultural and historical context that delineates the association between dance and rhetoric as it was understood by Quintilian, Sir Thomas Elyot, and Ben Jonson. Indeed, Perdita's corporeal eloquence communicates an air of nobility out of place in the rustic setting of this scene and misplaced within this assumed peasant. Because Perdita's true identity is discovered soon after (5.2), this scene, with its covert comingling of peasants and aristocrats and its graceful spectacle, can be understood as a pivotal moment that moves the play from its discordant beginning to its harmonious end.

Abstract Introduction: The Destiny Breast-04 Trial (DB-04) demonstrated the survival benefits of Trastuzumab Deruxtecan (T-DXd) for women with metastatic HER2 Low breast cancer, characterised by 1+ or 2+ IHC staining without amplification. While the DB-04 study applied the standard 2018 ASCO CAP IHC scoring criteria, in clinical practice, distinguishing HER2 0 from 1+ cancers is challenging as i) HER2 Low is not a biologically distinct subset of breast cancer, ii) there are no reference standards for HER2 Low cancers, iii) second-tier test, like ISH, are not applicable, and iv) there are no known controls for cases that have 0 or 1+ HER2 scores. For two decades this distinction was clinically immaterial, but now differentiating between HER2 0 and 1+ has now become crucial for determining patient eligibility for T-DXd therapy. Concerns regarding the subjectivity, imprecision and poor concordance between pathologists in scoring IHC in HER2 Low cancers raise the potential for misalignments in patient treatment. Ensuring pathologists have access to focused training for interpreting IHC scores at the low end of the HER2 expression spectrum, quality assurance procedures and reference sets are essential steps to help pathologists assess HER2 Low breast cancers more accurately and consistently. Design: In this study, a group of 9 experienced breast pathologists compiled a deidentified set of 60 breast cancer core biopsies from 3 laboratories. The Ventana 4B5 HER2 assay had been used for evaluation and the local laboratories had scored the samples as HER2 0 or 1+. We teased out the ASCO CAP 2018 criteria and used our collective expertise of reporting HER2 IHC for many years to specify HER2 Low-focused scoring conventions, including some potential pitfalls. Subsequently, using these conventions, each pathologist reviewed digitized whole slide images of the IHC slides and scored HER2 expression for each case. At a consensus workshop, the cases were jointly reviewed to establish consensus scores and determine the percentage of HER2-expressing tumor cells in each case. We then evaluated the concordance between individual pathologists' HER2 scores and the consensus opinion and ascertained reasons for discordance. Results: Among the cases discussed during the consensus conference, 43 out of 60 (71.7%) were classified as HER2 Low, with 40 cases designated as 1+ and three as 2+ (known to be not amplified). The consensus score matched the majority opinion of the pathologists' independent scores in 93.3% (56 out of 60) of the cases. Utilizing the HER2 Low-focused IHC scoring conventions, 7 out of 17 (41.2%) cases locally reported as HER2 0 were reclassified as HER2 Low. Conversely, among the 32 cases with local scores of 1+, 7 (21.8%) were reclassified as ultralow or null. When compared to the consensus score, individual pathologists' scores demonstrated concordance levels ranging from 71.7% to 91.7%, with a mean concordance rate of 81.3%. Cases with less than 20% of tumor cells expressing HER2 had lower inter observer concordance. This reference set of cases with expert consensus HER2 scores obtained through our study will be invaluable for peer training and the development of external quality assurance programs for HER2 Low cancers, including the quality assurance program of the Royal College of Pathologists of Australasia. Conclusion: This study revealed that when breast pathologists were provided explicit instructions on scoring pitfalls and HER2 Low-focused scoring conventions, their HER2 scores were concordant with expert consensus scores in 71.7% to 91.7% of cases. Discordant cases primarily involved cases with less than 20% of tumor cells expressing HER2. Utilising such an approach, peer training and quality assurance procedures will improve the accuracy and consistency of HER2 IHC assessment for better patient care. Reassessing older cases using HER2 Low focused scoring conventions may result in revisions of HER2 scores from HER2 Low to zero, and vice versa. Table. Individual pathologists' concordance with the consensus HER2 IHC score Applying our HER2 Low-focused IHC scoring conventions in a set of 60 core biopsies of invasive breast cancer with low or 0 HER2 protein expression. Citation Format: Gelareh Farshid, Beena Kumar, Nirmala Pathmanathan, Hema Mahajan, Ben Dessauvagie, Jane Armes, Cameron Snell, Amardeep Gilhotra. Improving HER2 Low Scoring Consistency and Accuracy: Insights from the Australian HER2 Low Concordance Study for Invasive Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-25-12.

Abstract Background: Circulating Tumor Cells (CTC) can be isolated in 40-80% of patients with metastatic breast cancer (MBC). High levels of CTC, defined as ≥5/7.5 ml of blood are associated with shorter progression-free survival and overall survival. CTC can be tested for clinically relevant biomarkers, such as ER, and HER2 status, and have the potential to guide therapy as well as help with disease monitoring. We investigated CTC detection rate, its correlation with clinical characteristics, pathological characteristics, and response to treatment in patients with any type of metastatic breast cancer who progressed on at least one line of therapy. Methods: Eligible patients with MBC were enrolled in the IMAGE-II study (Individualized Molecular Analyses Guide Efforts in Breast Cancer) NCT02965755, in which we obtained archival tissue as part of the standard of care, and prospectively collected serial blood samples for CTC analysis. We compared CTC levels and biomarker status with clinical factors, tissue-based pathology, and molecular biomarkers. We assessed whether changes in CTC count correlated with treatment response. Blood samples were collected at baseline (Day 1), after 1-2 weeks of therapy, after 8-12 weeks, and at subsequent restaging (every 8-12 weeks). Medical records were reviewed every 3 months for ongoing treatment response, and death. Samples were processed at the Biocept CLIA-certified Laboratory. CTC were enumerated by the presence of CD45- and DAPI+ cells. Further CTC characterization was performed by antibody staining of specific protein biomarkers (ER, HER2). Fisher’s exact test was used to evaluate the association between baseline CTC < 5 and ≥5/7.5ml with patient characteristics. McNemar’s test was used to assess discordance between tissue-based and CTC-defined markers. Results: Between 1/26/2018 and 12/31/22 baseline samples were collected from 70 women with a median age of 56 (36-82) who were enrolled at four study sites. CTC was detected in 59 (84%) of participants. Baseline CTC counts were < 5/7.5 ml in 37/59 (63%) and ≥5/7.5 ml in 22/59 (37%) of participants. Differences between breast cancer subtype and CTC-receptor status were observed (Table 1). Among the 41 patients who were ER-positive, 31 (76%) were CTC ER-negative(p< 0.001). Among 29 patients who were ER-negative, 4 (14%) were CTC ER-Positive (P< 0.001). Among the 7 patients who were HER2 positive, 2(29%) were HER2 positive on CTC. Among 63 patients who were HER2 negative, 7(11%) had HER2 expression on their CTC. The discordance in the classification of HER2 wasn't statistically significant (p=0.77). Elevated CTC at baseline was more frequently detected in younger participants (< 50 years old) (55% vs 27%; P=0.22), in Black women compared to White (60 % vs 29 %, P=0.27), and in participants with visceral vs non-visceral metastasis (52% vs 28 %, P=0.40). Patients with CTC ≥5 vs < 5/7.5mL at baseline had a shorter duration of anti-HER2-based therapy (61.5 vs 836 days, p=0.04). There were no statistically significant differences among participants who received chemotherapy agents (316.5 vs 365.5 days, P=0.88), endocrine therapy (376 vs 490 days, P=0.89), or overall therapy (272 vs 390 days, P=0.21). Conclusions: We observed significant differences in the expression of ER between tumor tissue and CTC, which can be partly due to tumor evolution over time. Additionally, participants who are young, Black, and those who have visceral metastasis may have higher CTC counts. Higher CTC counts were associated with a shorter duration of anti-HER2 therapy. Although it didn’t meet statistical significance, a similar trend was observed in patients who received chemotherapy and endocrine therapy. Table 1: MBC Tissue-Based Subtype and CTC-receptor status at baseline Citation Format: Asnakech Bayable, Tingchang Wang, Amanda Blackford, Jessica Tao, Jenna Canzoniero, Seoho Lee, Faith Too, Barbara Blouw, Mary Wilkinson, Rima Couzi, Antonio Wolff, Christie Hiton, Ben Park, Vered Stearns, Cesar Santa-Maria. Correlation of Circulating Tumor Cells (CTC) with Clinical Characteristics, Pathological Factors, and Treatment Response in Patients with Metastatic Breast Cancer (MBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-16-02.

Abstract Introduction The CD30 antigen is expressed by a small number of cells in classical Hodgkin lymphoma (HL), by malignant cells in anaplastic large cell lymphoma (ALCL), and in several non-Hodgkin lymphomas (NHL). Brentuximab vedotin (BV), an anti-CD30 monoclonal antibody (Ab) conjugated to chemotherapy, showed its efficacy in HL and ALCL. However, a correlation between response to BV and CD30 expression in NHL is difficult to establish by immunohistochemistry (IHC) since the count of dimly positive cells is difficult to standardize. Flow cytometry (FCM) is a standardizable tool which allows the multiparametric characterization of malignant NHL cells and the quantification of proteins at the cell surface. The objective of this multicentric study is to standardize CD30 expression in NHL by quantitative FCM. Materiel and methods The nine centers used one or two cytometers: BD Biosciences (BD) n=7, Beckman Coulter (BC) n=4. The standardization was conducted using the Euroflow strategy, the same operating procedure and the same reagents. Abs recognizing different CD30 epitopes were: BerH83 (BD), HRS4 (BC) and a specific AC10 (Ancell) similar to BV. If tissue was available, pathologists locally used BerH2 (Dako) for IHC. The CD30 expression was normalized using Mean Fluorescence Intensity (MFI) to MFI CD4 expression and expressed as a percentage (nMFI30). Three cell lines (SUDHL4, K562 and L82) with differential expression of CD30 were shipped to the different laboratories in order to validate the centers using a robust statistical method. Then, NHL cases including anaplastic lymphomas, T lymphomas, and large B cell lymphomas were collected using a website www.mfi30.fr. All FCM Abs were used on available cells when nMFI30 >1% using Ancell Ab. Results On cell lines, all centers obtained similar results: z-scores between -2 to +2. Mean of nMFI30 were SUDHL4 0.1% (SD=0.1), K562 69.8% (SD=16.9), L82 292.9% (SD= 45.7) with BD Abs and 0.6% (SD=0.1), 229.9% (SD= 47.9) and 2053.8 (SD= 282) with BC Abs , respectively, demonstrating that BD and BC Abs are not equivalent. Samples from 82 adult patients were included in the study: peripheral blood (n=39), lymph node suspensions (n=21), bone marrow (n=5) or different tissues (n=17, cerebrospinal, seroma, pleural and ascite fluid, spleen). The diagnoses included diffuse large B-cell lymphoma (DLCBL, n=33 with 4 DLBCL of central nervous system (CNS)), Sezary syndrome (SS, n=14), peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS, n=11), T-cell prolymphocytic leukaemia (T-PLL, n=8), enteropathy-associated T-cell lymphoma (EATL-1, n=2), angio-immunoblastic lymphoma (AITL, n=5), primary effusion lymphoma (PEL, n=1), plasmablastic lymphoma (PBL, n=1), B-lymphoblastic lymphoma (B-LBL, n=1), breast implant associated anaplastic large cell lymphoma (BIA-ALCL, n=1), anaplastic large cell lymphoma (ALCL, n=1), mantle cell lymphoma (n=1), T-cell large granular lymphocyte leukemia (T-LGLL, n=2) and chronic lymphoproliferative disorders of NK cells (CLPD-NK, n=1). Four groups are defined: (1) a negative group (n=60) presents nMFI30 <1% using Ancell Ab. In this group, IHC is negative except in 1 case of PTCL-NOS; (2) a small highly positive group (n=4) presents nMFI30 >10% with the 3 FCM Abs and positive in IHC (2 ALCL, 1 DLBCL, 1 EATL). This group shows a more intense nMFI30 with BC Ab; (3) a dim positive group (n=8) presents nMFI30 between 1-10% with the 3 FCM Abs. In this group, IHC is negative in 2 out of the 3 tested cases; (4) a discordant group (n=10) presents nMFI30 >1% with at least 1 Ab and discordant with another one. In this group, 8 IHC were tested: 2 IHC positive <1% only with BD Ab, 5 IHC negative cases only >1% with Ancell Ab and 1 case shows a high discrepancy between 2 FCM Abs. Regarding lymphoma entities, T-PLL, DLBCL-CNS, and T-LGLL are always negative and the ALCL are positive. Seven out of the 33 DLBCL are in the positive or discordant groups (21%). Conclusion As previously reported in literature using IHC, CD30 is positive in all ALCL, in some DLCBL (20%) and only rarely in other NHL using FCM. Therefore these first results emphasize the feasibility of FCM in CD30 determination and quantification in NHL subtypes and mainly its multicentric standardization. The inclusion of FCM with relevant Abs in clinical trials using BV should be now validated in larger series to better understand clinical results. Figure. Figure. Disclosures Pruvot Debliquis: Alexion: Consultancy, Honoraria; Takeda Oncology: Honoraria. Baseggio:Takeda Oncology: Honoraria. Jacob:Takeda Oncology: Honoraria. Drenou:Takeda Oncology: Honoraria, Research Funding; Alexion: Consultancy, Honoraria.

Összefoglaló. Bevezetés és célkitűzés: A gyakori autoszomális trisomiák és a nemi kromoszómaeltérések a mikroszkóppal észlelhető kromoszóma-rendellenességek kb. 80–85%-át képviselik. A ritka kromoszóma-rendellenességek klinikai következménye jelentős, kimutatásukat a jelenlegi szűrővizsgálatok ugyan nem célozzák, de a teljes kromoszómaszerelvényt vizsgáló, nem invazív praenatalis tesztelés új lehetőséget nyitott a korai felismerésükre. Módszer: Retrospektív analízis (2014–2019) a mikroszkóppal kimutatható kromoszóma-rendellenességek eloszlására, a fetoplacentaris mozaikosság előfordulására, klinikai összefüggéseire a praenatalis vizsgálatok tükrében egy hazai tercier centrumban. Eredmények: 2504 invazív beavatkozást végeztünk és 200 kromoszómaeltérést mutattunk ki (8%), melyek közül újonnan kialakult, ritka rendellenesség 27 volt (13,5%). Ritka autoszomális trisomia 14, poliploidia 6, de novo szerkezeti kromoszómaeltérés 5, marker kromoszóma 2 esetben igazolódott. A fetoplacentaris mozaikosság aránya a gyakori/ritka kromoszómaeltérésekben 12,4%/77,8% volt (p = 0,001), 17/40 esetben lepényre korlátozódott. A gyakori trisomiákkal kóros tarkóredő-vastagság 58%-ban, major ultrahangeltérés 35%-ban társult, melyek jelentősen különböztek a ritka kromoszómaeltérésekben (11%, p = 0,006; 67%, p = 0,047). A ritka kromoszómaeltérések jellemző praenatalis major ultrahangeltérése a facialis dysmorphismus volt. A teljes kromoszómaszerelvényt vizsgáló praenatalis tesztelés a ritka kromoszómaeltérések 12 lepényi mozaikos esetében (44%) feltételezhetően álpozitív, 1 esetben (3,7%) álnegatív eredményt generált volna, miközben a ritka autoszomális trisomiák 2 esetében ultrahangeltérés nélkül is korán detektálta volna a ritka magzati kromoszómaeltérést (7,4%). Következtetés: A normális tarkóredő-vastagság esetén észlelt major ultrahangeltérések felhívhatják a figyelmet a döntően mozaikos ritka kromoszóma-rendellenességekre. A teljes kromoszómaszerelvényt vizsgáló, nem invazív szűrőteszt a korai diagnosztika alternatívája lehet, a mozaikosságból adódó álpozitív eredményekre azonban számítani kell. A fetoplacentaris mozaikosság ismerete fontos klinikai információt biztosít, mely befolyásolhatja a terhesség kimenetelét, a terhesség követésének módját. A pontos citogenetikai karakterizálás elengedhetetlen. Orv Hetil. 2021; 162(29): 1156–1165. Summary. Introduction and objective: To determine the prevalence of microscopically visible de novo atypical chromosomal aberrations and fetoplacental mosaicism in a prenatal tertial referral center, and to investigate the maternal and fetal characteristics in connection with genomewide non-invasive prenatal screening. Method: Retrospective cohort study from 2014 to 2019 of pregnancies with invasive genetic analysis. Results: In the cohort of 2504 cases, the proportion of CVS was 53.3%. We diagnosed 200 chromosomal aberrations (8%), including 13.5% of de novo rare chromosomal aberrations (14 rare autosomal trisomies, 6 polyploidies, 5 structural aberrations and 2 small supernumerary marker chromosomes). The rate of fetoplacental mosaicism was 12.4%/77.8% in common/atypical chromosomal aberrations (p = 0.001) and confined to placenta in 17/40 cases. Associated ultrasound abnormalities were abnormal nuchal translucency and major malformations in 58% and 35% with common trisomies and 11% (p = 0.006) and 67% (p = 0.047) with true mosaic cases of rare abnormalities, respectively. Major ultrasound malformation was facial dysmorphism with rare aberrations. Potential application of genomewide non-invasive prenatal test in atypical chromosomal aberrations presumably would have been false-positive in 12 cases (44%), false-negative in 1 case (3.7%), and would have early detected 2 cases of rare autosomal trisomies (7.4%) without ultrasound anomalies. Conclusion: Structural ultrasound malformations with normal nuchal translucency thickness may be indicative of rare chromosomal aberrations. Application of genomewide non-invasive prenatal test is an alternative of early diagnostic methods with a potential of discordant results due to mosaicism. Knowledge about the presence of fetoplacental mosaicism influences risk estimation and genetic counseling, detailed cytogenetic characterization is of utmost importance. Orv Hetil. 2021; 162(29): 1156–1165.

DNA barcoding is a technique in which identification of species using DNA barcodes. We generated a verified reference library of cytochrome c oxidase subunit I (COI) sequences for 226 barcodes belonging to 83 fish species from 67 genera, 39 families and 21 orders of fishes with the average divergence within a species is 010%, 13.57% within a genus, and 17.33% within a family with 97-100% identity with comparison to the Genbank database and BOLD of the Chilika lagoon, India. Data analysis done by barcode gap analysis, barcode index number and automatic barcode gap discovery to discriminate the species up to 97.53%, 93.90% and 95.06% respectively. The Barcode Index Number (BIN) discordance analysis reflected 226 specimens belongs to 83 BINs, of which 73.49%were taxonomically concordant and 26.50% were singletons and absence of discordant BIN in our dataset. Finally, the identification success rate of DNA barcoding was evaluated based on the sequencing success rate and species discrimination rate.

AbstractUzbekistan is one of two doubly landlocked countries in the world, where all rivers are endorheic basins. Although fish diversity is relatively poor in Uzbekistan, the fish fauna of the region has not yet been fully studied. The aim of this study was to establish a reliable barcoding reference database for fish in Uzbekistan. A total of 666 specimens, belonging to 59 species within 39 genera, 17 families, and 9 orders, were subjected to polymerase chain reaction amplification in the barcode region and sequenced. The length of the 666 barcodes was 682 bp. The average K2P distances within species, genera, and families were 0.22%, 6.33%, and 16.46%, respectively. The average interspecific distance was approximately 28.8 times higher than the mean intraspecific distance. The Barcode Index Number (BIN) discordance report showed that 666 specimens represented 55 BINs, of which five were singletons, 45 were taxonomically concordant, and five were taxonomically discordant. The barcode gap analysis demonstrated that 89.3% of the fish species examined could be discriminated by DNA barcoding. These results provide new insights into fish diversity in the inland waters of Uzbekistan and can provide a basis for the development of further studies on fish fauna.

t The diversity of freshwater fish in the state of Telangana is currently recorded as 143 species under 34 families and 14 orders. The current study principally deals with the identification of fish fauna based on morphology and the generation of DNA barcode data. DNA sequence data on a partial segment of the mitochondrial cytochrome oxidase C subunit I (mtCOI) gene were generated from freshwater fishes sampled from various localities within the state of Telangana. The study identified 57 species under 41 genera, 24 families, and 11 orders. Morphological identification was concordant with the molecular basis of taxon assignment, where 57 OTU (Operational Taxonomic Units) correspond to 57 species, and no BIN discordance was found in the dataset. The present phylogenetic tree discriminates all the studied species based on the partial mtCOI gene. The study contributed DNA sequence data for many of the important species for the first time to the global database

Reference libraries of DNA sequences are the backbone of DNA-based taxonomic identification systems. The quality and accuracy of the data in reference libraries is critical to achieve reliable identifications. Faulty or inaccurate data may have detrimental impacts in various downstream applications, perpetuating errors over long-term studies and biodiversity data repositories. This risk is particularly prevalent in metabarcoding approaches, where millions of sequences are assigned to taxa in reference libraries through automated and frequently unsupervised procedures. Although quality-compliance measures have been implemented in several stages of the DNA barcode production workflow, no systematized approach has tackled the challenges of revision, curation and annotation of reference libraries. The trend for increasing detection of cryptic diversity further complicates this task. Here we outline the conclusions of the application of two distinct approaches to audit and annotate reference libraries: the hackathon on marine invertebrates hosted by the 8th IBOL conference, and the bioinformatics application “Barcode, Audit & Grade System” (BAGS; Fontes et al. 2021). The former consisted on the assembly of 18 researchers involved in marine barcoding, aiming to audit and annotate a very large number DNA barcode records available in BOLD from major marine invertebrate taxa, including all or selected groups of Annelida, Crustacea, Echinodermata and Mollusca. Discordant Barcode Index Numbers (BINs), that is, BINs including more than one species, were reviewed individually, and the respective records annotated with one of the 4 following tags: MIS-ID (misidentification); AMBIG (ambiguous, unable to resolve); COMPLEX (multiple BINs); SHARE (barcodes shared among species in the same BIN). This effort resulted in the processing of >80.000 barcodes, corresponding to >7.500 species, of which 7% were tagged MIS-ID, 17% AMBIG, 13% COMPLEX and 1% SHARE, with Gastropoda displaying particularly high levels of ambiguity. The sizeable portion of MIS-ID and AMBIG tags raises concern. Yet, part of the AMBIG tags merely reflect underlying uncertainty in species taxonomic status, rather than the deposition of erroneous data in BOLD. Hence, in addition to auditing and annotation, extensive effort should continue to be allocated to the underpinning alpha taxonomy of reference libraries. The second approach here described is BAGS, which consists on an R-based application that provides an user-friendly platform for automated auditing of user-selected metazoan cytochrome oxidase I (COI) reference libraries. BAGS sorts BOLD’s records and species into 5 grades, depending on whether they display BIN concordance (A, B) multiple BINs (C), less than two records (D) or discordant BINs (E). A WoRMS-linked filter allows to select or exclude marine taxa, and a reporting component provides a graphical overview and FASTA files assorted in different combinations of grades. Therefore, BAGS can provide a quick appraisal of the status of an user-defined reference library, allowing simultaneously to recognize the most reliable records, the incidence of cases high intraspecific divergence, gaps in representativeness, and inaccuracies of potential concern. A pilot assessment of BAGS performance in three datasets comprising marine fish, Chironomidae (Insecta) and marine Amphipoda (Crustacea) highlighted the differences in the congruence status of the respective reference libraries. In conclusion, the hackathon had and expressive contribution to the revision and annotation of a very large number of marine invertebrate records lodged in BOLD. Human-mediated revision is highly-reliable and consequential, however, it constituted a massive undertaking that can hardly be repeated without a previous refinement and substantial reduction of the datasets to be revised. This could be achieved resorting to automated revision systems, among which BAGS constitutes a first step. We intend to progress with the expansion and improvement of BAGS, namely by introducing further refinements in the analyses of grade E data, in order to automatically discard simple cases of discordance, thereby reducing the amount of data needing human-mediated revision. Recognition of the need for automated reference library auditing and curation systems is essential to raise confidence of researchers, environmental managers and governmental agencies for the adoption and implementation of DNA-based approaches in aquatic biomonitoring.

Gracillariidae is the most species-rich leaf-mining moth family with over 2,000 described species worldwide. In Europe, there are 263 valid named species recognized, many of which are difficult to identify using morphology only. Here we explore the use of DNA barcodes as a tool for identification and species discovery in European gracillariids. We present a barcode library including 6,791 COI sequences representing 242 of the 263 (92%) resident species. Our results indicate high congruence between morphology and barcodes with 91.3% (221/242) of European species forming monophyletic clades that can be identified accurately using barcodes alone. The remaining 8.7% represent cases of non-monophyly making their identification uncertain using barcodes. Species discrimination based on the Barcode Index Number system (BIN) was successful for 93% of species with 7% of species sharing BINs. We discovered as many as 21 undescribed candidate species, of which six were confirmed from an integrative approach; the other 15 require additional material and study to confirm preliminary evidence. Most of these new candidate species are found in mountainous regions of Mediterranean countries, the South-Eastern Alps and the Balkans, with nine candidate species found only on islands. In addition, 13 species were classified as deep conspecific lineages, comprising a total of 27 BINs with no intraspecific morphological differences found, and no known ecological differentiation. Double-digest restriction-site associated DNA sequencing (ddRAD) analysis showed strong mitonuclear discrepancy in four out of five species studied. This discordance is not explained by Wolbachia-mediated genetic sweeps. Finally, 26 species were classified as “unassessed species splits” containing 71 BINs and some involving geographical isolation or ecological specialization that will require further study to test whether they represent new cryptic species.

Sex discordance between cell-free DNA (cfDNA) testing and ultrasound examination is rare but can cause significant patient discomfort and uncertainty. Here, we present two clinical cases where a closer examination of raw sequencing data allowed us to anticipate possible discrepancies caused by the insertion of Y-chromosome regions into the maternal genome. We used Illumina’s VeriSeq NIPT Solution v2 and a proprietary bioinformatics pipeline to analyze cfDNA in the maternal bloodstream. Paired-end sequencing data were aligned to the reference genome (hg19). Non-duplicated aligned reads were aggregated into 100-kb bins, adjusted for CG bias, and further aggregated into 5-Mb windows. Z-scores were calculated for autosomes, sex chromosomes, and 5-Mb bins. The two clinical cases were classified as low-risk male fetuses according to the primary statistics (case A: NCVx = 0.3; NCVy = 40.6; native fetal fraction (FFi) = 5.1%, and case B: NCVx = −0.3, NCVy = 40.7, FFi = 10.8%); however, the Y-chromosome-based FF (FFy) was significantly lower than the default FF estimate (FFy ≅ 2% in both cases). Plots of X and Y chromosome Z-scores for each 5-Mb bin, according to genomic position, identified bins with Z-scores significantly higher than those expected for any pregnancy with a male fetus. The genomic coordinates of these bins overlapped with the amelogenin (AMELY) and protein kinase Y-linked (PRKY) genes, respectively. Amplification of these regions in the DNA isolated from the white blood cells fraction confirmed the presence of Y-chromosome insertions in the maternal genome. This study highlights a new source of discrepancy in cfDNA testing due to maternal genomic variations. These findings suggest the need for improvements to current bioinformatics pipelines to identify and exclude possible maternal perturbations from the classification algorithms used for aneuploidy and sex calls.

Introduction and Objective: Body mass index (BMI), weight adjusted for height, is an imprecise tool for the diagnosis of obesity. Body composition assessment with bioelectric impedance analysis (BIA) scales estimate fat mass and % adiposity, offering a more precise diagnosis of obesity. The objective of this project was to compare the use of BMI and BIA scale assessment of % adiposity for the diagnosis of obesity. Methods: Obesity status was determined by both traditional BMI and BIA scale in our weight management clinic. BMI (kg/m2) was calculated from weight and height measured by stadiometer. Body composition was assessed with TANITA BIA scale MC-780U. Body composition measures included total body water, fat, muscle and bone mass, and % adiposity. BMI classification of obesity was as follows: obese BMI ≥ 30 kg/m2, overweight BMI 25 - 29.9 kg/m2, normal BMI 18.6 - 24.9 kg/m2. Classification of obesity by BIA % adiposity was: women ≥ 33%, men >25%. Concordance between BMI and BIA assessments for the diagnosis of obesity was analyzed. Results: Of 112 patients assessed, 87% were female, 49% non-Hispanic white, 43% black. Mean age was 49±13 years, BMI 36.4±7.7 kg/m2, and % adiposity 40.3±8.2%. BMI classification diagnosed 81.2% (n=91) with obesity, 12.5% (n=14) overweight, and 6.2% (n=7) normal. BIA % adiposity score diagnosed 83.9% (n=94) with obesity. The diagnosis of obesity was concordant between BMI and BIA classification in 87.5% (n=98). Of 14 discordant cases, 86% (n=12) were female; 64% were middle age 39-59 years. Eight were classified as obese by BIA but not BMI. Six were classified as obese by BMI but not BIA. Conclusion: Assessment of adiposity by BIA scale offers an accurate measure of total and percent adiposity that more precisely classifies patients as obese than traditional BMI measures calculated from height and weight alone. Discordance between the two different measures raises concern for misclassification of obesity status which may over or underestimate related health risks. Disclosure A. Johnson-Jennings: None. A.D. Coviello: Advisory Panel; Novo Nordisk. Consultant; Intuitive Surgical. Other Relationship; GI Dynamics. Consultant; Hanmi Pharm. Co., Ltd. Advisory Panel; NewAmsterdam Pharma.

Abstract Whole-exome sequencing (WES) has been widely used to study the role of protein-coding variants in genetic diseases. Non-coding regions, typically covered by sparse off-target data, are often discarded by conventional WES analyses. Here, we develop a genotype calling pipeline named WEScall to analyse both target and off-target data. We leverage linkage disequilibrium shared within study samples and from an external reference panel to improve genotyping accuracy. In an application to WES of 2527 Chinese and Malays, WEScall can reduce the genotype discordance rate from 0.26% (SE= 6.4 × 10−6) to 0.08% (SE = 3.6 × 10−6) across 1.1 million single nucleotide polymorphisms (SNPs) in the deeply sequenced target regions. Furthermore, we obtain genotypes at 0.70% (SE = 3.0 × 10−6) discordance rate across 5.2 million off-target SNPs, which had ~1.2× mean sequencing depth. Using this dataset, we perform genome-wide association studies of 10 metabolic traits. Despite of our small sample size, we identify 10 loci at genome-wide significance (P < 5 × 10−8), including eight well-established loci. The two novel loci, both associated with glycated haemoglobin levels, are GPATCH8-SLC4A1 (rs369762319, P = 2.56 × 10−12) and ROR2 (rs1201042, P = 3.24 × 10−8). Finally, using summary statistics from UK Biobank and Biobank Japan, we show that polygenic risk prediction can be significantly improved for six out of nine traits by incorporating off-target data (P < 0.01). These results demonstrate WEScall as a useful tool to facilitate WES studies with decent amounts of off-target data.

Abstract Unsupervised feature selection is a critical step for efficient and accurate analysis of single-cell RNA-seq data. Previous benchmarks used two different criteria to compare feature selection methods: (i) proportion of ground-truth marker genes included in the selected features and (ii) accuracy of cell clustering using ground-truth cell types. Here, we systematically compare the performance of 11 feature selection methods for both criteria. We first demonstrate the discordance between these criteria and suggest using the latter. We then compare the distribution of selected genes in their means between feature selection methods. We show that lowly expressed genes exhibit seriously high coefficients of variation and are mostly excluded by high-performance methods. In particular, high-deviation- and high-expression-based methods outperform the widely used in Seurat package in clustering cells and data visualization. We further show they also enable a clear separation of the same cell type from different tissues as well as accurate estimation of cell trajectories.

With the increasing precision of recent cosmological surveys and the discovery of important tensions within the ΛCDM paradigm, it is becoming more and more important to develop tools to quantify accurately the discordance between different probes. One such tool is the Surprise statistic, a measure based on the Kullback-Leibler divergence. The Surprise, however, has been up to now applied only under its Gaussian approximation, which can fail to properly capture discordance in cases that deviate significantly from Gaussianity. In this paper we developed the code which computes the full numerical non-Gaussian Surprise, and analyse the Surprise for BAO + BBN and supernova data. We test different cosmological models, some of which the parameters deviate significantly from Gaussianity. We find that the non-Gaussianities, mainly present in the Supernova dataset, change the Surprise values significantly from its Gaussian approximation, and reveal a borderline 2.0σ tension in the curved wCDM model (o wCDM) between the combined Pantheon+ and SH0ES (Pantheon+&SH0ES) data and the dataset which combines SDSS, BOSS and eBOSS BAO. This modest tension is hidden in the Gaussian Surprise approximation. For DESI, the discrepancy with Pantheon+&SH0ES is at the 1.5σ level for o wCDM, but a large 3.4σ for ΛCDM. Removing SH0ES data drops this significance to 2.6σ.

Abstract RNA-sequencing enables accurate and low-cost transcriptome-wide detection. However, expression estimates vary as reference genomes and gene annotations are updated, confounding existing expression-based prognostic signatures. Herein, prognostic 9-gene pair signature (GPS) was applied to 197 patients with stage I lung adenocarcinoma derived from previous and latest data from The Cancer Genome Atlas (TCGA) processed with different reference genomes and annotations. For 9-GPS, 6.6% of patients exhibited discordant risk classifications between the two TCGA versions. Similar results were observed for other prognostic signatures, including IRGPI, 15-gene and ORACLE. We found that conflicting annotations for gene length and overlap were the major cause of their discordant risk classification. Therefore, we constructed a prognostic 40-GPS based on stable genes across GENCODE v20-v30 and validated it using public data of 471 stage I samples (log-rank P < 0.0010). Risk classification was still stable in RNA-sequencing data processed with the newest GENCODE v32 versus GENCODE v20–v30. Specifically, 40-GPS could predict survival for 30 stage I samples with formalin-fixed paraffin-embedded tissues (log-rank P = 0.0177). In conclusion, this method overcomes the vulnerability of existing prognostic signatures due to reference genome and annotation updates. 40-GPS may offer individualized clinical applications due to its prognostic accuracy and classification stability.

Abstract The objective of this study was to understand and measure epigenetic changes associated with the occurrence of CHDs by utilizing the discordant monozygotic twin model. A unique set of monozygotic twins discordant for double-outlet right ventricles (DORVs) was used for this multiomics study. The cardiac and muscle tissue samples from the twins were subjected to whole genome sequencing, whole genome bisulfite sequencing, RNA-sequencing and liquid chromatography-tandem mass spectrometry analysis. Sporadic DORV cases and control fetuses were used for validation. Global hypomethylation status was observed in heart tissue samples from the affected twins. Among 36,228 differentially methylated regions (DMRs), 1097 DMRs involving 1039 genes were located in promoter regions. A total of 419 genes, and lncRNA–mRNA pairs involved 30 genes, and 62 proteins were significantly differentially expressed. Multiple omics integrative analysis revealed that five genes, including BGN, COL1A1, COL3A1, FBLN5, and FLAN, and three pathways, including ECM-receptor interaction, focal adhesion and TGF-β signaling pathway, exhibited differences at all three levels. This study demonstrates a multiomics profile of discordant twins and explores the possible mechanism of DORV development. Global hypomethylation might be associated with the risk of CHDs. Specific genes and specific pathways, particularly those involving ECM–receptor interaction, focal adhesion and TGF–β signaling, might be involved in the occurrence of CHDs.

Abstract Whole-genome sequencing (WGS) of parent–offspring trios has become widely used to identify causal copy number variations (CNVs) in rare and complex diseases. Existing CNV detection approaches usually do not make effective use of Mendelian inheritance in parent–offspring trios and yield low accuracy. In this study, we propose a novel integrated approach, TrioCNV2, for jointly detecting CNVs from WGS data of the parent–offspring trio. TrioCNV2 first makes use of the read depth and discordant read pairs to infer approximate locations of CNVs and then employs the split read and local de novo assembly approaches to refine the breakpoints. We use the real WGS data of two parent–offspring trios to demonstrate TrioCNV2’s performance and compare it with other CNV detection approaches. The software TrioCNV2 is implemented using a combination of Java and R and is freely available from the website at https://github.com/yongzhuang/TrioCNV2.

Abstract Structural variant (SV) detection is essential for genomic studies, and long-read sequencing technologies have advanced our capacity to detect SVs directly from read or de novo assembly, also known as read-based and assembly-based strategy. However, to date, no independent studies have compared and benchmarked the two strategies. Here, on the basis of SVs detected by 20 read-based and eight assembly-based detection pipelines from six datasets of HG002 genome, we investigated the factors that influence the two strategies and assessed their performance with well-curated SVs. We found that up to 80% of the SVs could be detected by both strategies among different long-read datasets, whereas variant type, size, and breakpoint detected by read-based strategy were greatly affected by aligners. For the high-confident insertions and deletions at non-tandem repeat regions, a remarkable subset of them (82% in assembly-based calls and 93% in read-based calls), accounting for around 4000 SVs, could be captured by both reads and assemblies. However, discordance between two strategies was largely caused by complex SVs and inversions, which resulted from inconsistent alignment of reads and assemblies at these loci. Finally, benchmarking with SVs at medically relevant genes, the recall of read-based strategy reached 77% on 5X coverage data, whereas assembly-based strategy required 20X coverage data to achieve similar performance. Therefore, integrating SVs from read and assembly is suggested for general-purpose detection because of inconsistently detected complex SVs and inversions, whereas assembly-based strategy is optional for applications with limited resources.

Abstract Chemosensitivity assays are commonly used for preclinical drug discovery and clinical trial optimization. However, data from independent assays are often discordant, largely attributed to uncharacterized variation in the experimental materials and protocols. We report here the launching of Minimal Information for Chemosensitivity Assays (MICHA), accessed via https://micha-protocol.org. Distinguished from existing efforts that are often lacking support from data integration tools, MICHA can automatically extract publicly available information to facilitate the assay annotation including: 1) compounds, 2) samples, 3) reagents and 4) data processing methods. For example, MICHA provides an integrative web server and database to obtain compound annotation including chemical structures, targets and disease indications. In addition, the annotation of cell line samples, assay protocols and literature references can be greatly eased by retrieving manually curated catalogues. Once the annotation is complete, MICHA can export a report that conforms to the FAIR principle (Findable, Accessible, Interoperable and Reusable) of drug screening studies. To consolidate the utility of MICHA, we provide FAIRified protocols from five major cancer drug screening studies as well as six recently conducted COVID-19 studies. With the MICHA web server and database, we envisage a wider adoption of a community-driven effort to improve the open access of drug sensitivity assays.

Abstract Introduction In May 2020, the United Kingdom banned menthol as a characteristic flavor in cigarettes. This study aimed to test cigarettes on sale in England in 2021–2022 for menthol and other characterizing flavors, through sensory and chemical testing. Aims and Methods Assessments were conducted for 20 cigarette brands (16 tests and four reference products). An untrained consumer panel of 50 people who smoked daily were each randomized to smell one of the two blocks of 10 unburnt cigarettes in duplicate (50 assessments per product). Using the Check-All-That-Apply method, participants assessed the presence of 22 odor attributes, including menthol/mint. For each test and reference cigarette, proportions of assessments that identified menthol/mint, “fruity,” “confectionary” and “non-tobacco” odors were identified and compared accounting for the within-participant duplicate testing. For each cigarette, the content of 34 flavoring chemicals (16 cooling/minty) was analyzed using gas chromatography-mass spectrometry. Results Four of the sixteen test cigarette products were more frequently identified by participants as having a menthol/mint odor than reference products and had detectable levels of menthol/mint in the chemical tests. For four other test products, there was some discordance between the chemical and sensory assessments. Sensory testing also identified a fruity odor in six test products and a confectionary odor in one test product. The compounds dihydroxyacetone and triacetin were detected above the LLOQ in all products. Conclusions Four cigarette products for sale in England in 2021–2022 appeared non-compliant with the ban on menthol as a characterizing flavor in sensory and chemical tests. Implications Menthol is known to enhance the appeal of tobacco products, particularly among young people. The subjective nature of determining “characterizing” flavors in tobacco products creates compliance challenges. Our findings suggest that more stringent regulatory policies around flavoring additives used in tobacco products might be necessary. An outright ban on menthol, other minty flavorings, and additives not essential to the manufacturing process could provide clearer guidelines for manufacturers and regulators.

Abstract Monochorionic twin pregnancies are a subset of twin pregnancies that face potential complications related to a shared circulation between the fetuses. These complications are related to anastomotic placental vessels connecting the cardiovascular systems of the two fetuses, which can result in significant sequela if one twin experiences intrauterine death. The sudden cardiovascular collapse in this scenario leads to a massive blood shift away from the healthy co-twin, significantly jeopardizing its life and long-term neurodevelopmental outcome. Such conditions include selective fetal growth restriction with abnormal Doppler findings, twin-twin transfusion with impending death in one twin and discordant fetal anomalies, for which fetal interventions are ineffective in improving outcomes or preventing the imminent death of the abnormal twin. Obstetricians have a professional obligation to respect the autonomy of pregnant patients and to maximize beneficence-based obligations to both pregnant and fetal patients. The goal of a selective termination is to maximize the health and life of the surviving fetal patient. It is recommended that policymakers consider including selective termination as an exemption to abortion ban laws.

AbstractBody composition is a key component of health in both individuals and populations, and excess adiposity is associated with an increased risk of developing chronic diseases. Body mass index (BMI) and other clinical or commercially available tools for quantifying body fat (BF) such as DXA, MRI, CT, and photonic scanners (3DPS) are often inaccurate, cost prohibitive, or cumbersome to use. The aim of the current study was to evaluate the performance of a novel automated computer vision method, visual body composition (VBC), that uses two-dimensional photographs captured via a conventional smartphone camera to estimate percentage total body fat (%BF). The VBC algorithm is based on a state-of-the-art convolutional neural network (CNN). The hypothesis is that VBC yields better accuracy than other consumer-grade fat measurements devices. 134 healthy adults ranging in age (21–76 years), sex (61.2% women), race (60.4% White; 23.9% Black), and body mass index (BMI, 18.5–51.6 kg/m2) were evaluated at two clinical sites (N = 64 at MGH, N = 70 at PBRC). Each participant had %BF measured with VBC, three consumer and two professional bioimpedance analysis (BIA) systems. The PBRC participants also had air displacement plethysmography (ADP) measured. %BF measured by dual-energy x-ray absorptiometry (DXA) was set as the reference against which all other %BF measurements were compared. To test our scientific hypothesis we run multiple, pair-wise Wilcoxon signed rank tests where we compare each competing measurement tool (VBC, BIA, …) with respect to the same ground-truth (DXA). Relative to DXA, VBC had the lowest mean absolute error and standard deviation (2.16 ± 1.54%) compared to all of the other evaluated methods (p < 0.05 for all comparisons). %BF measured by VBC also had good concordance with DXA (Lin’s concordance correlation coefficient, CCC: all 0.96; women 0.93; men 0.94), whereas BMI had very poor concordance (CCC: all 0.45; women 0.40; men 0.74). Bland-Altman analysis of VBC revealed the tightest limits of agreement (LOA) and absence of significant bias relative to DXA (bias −0.42%, R2 = 0.03; p = 0.062; LOA −5.5% to +4.7%), whereas all other evaluated methods had significant (p < 0.01) bias and wider limits of agreement. Bias in Bland-Altman analyses is defined as the discordance between the y = 0 axis and the regressed line computed from the data in the plot. In this first validation study of a novel, accessible, and easy-to-use system, VBC body fat estimates were accurate and without significant bias compared to DXA as the reference; VBC performance exceeded those of all other BIA and ADP methods evaluated. The wide availability of smartphones suggests that the VBC method for evaluating %BF could play an important role in quantifying adiposity levels in a wide range of settings.Trial registration: ClinicalTrials.gov Identifier: NCT04854421.

El pensamiento evolutivo debería enseñarse como un programa que integra lo vivo y que ofrece explicaciones en distintas áreas del desarrollo humano; sin embargo, no es así. En México, el bachillerato es el último nivel formal en donde se puede contribuir a la alfabetización científica del ciudadano; quien podría comprender diversos fenómenos de importancia, tales como la resistencia bacteriana a los antibióticos, las dificultades encontradas en el control de pandemias, como el VIH, entender el origen y transformación de los virus, como el SARS-CoV 19, entre otros. Considerando esa importancia, el objetivo de este trabajo es identificar la concordancia entre los aprendizajes constructivistas esperados sobre evolución biológica de los planes de estudio de educación básica (secundaria y nivel medio superior) y los instrumentos de evaluación que se utilizan a través del análisis de las preguntas formuladas en las principales guías de exámenes de admisión al nivel medio superior en México. La metodología se basó en hacer una revisión de los planes de estudio actuales; así como del fundamento y lineamientos del examen de admisión realizado por el CENEVAL. Se recopilaron las preguntas sobre evolución de la Guía del Examen Nacional de Ingreso a la Educación Media Superior (EXANI-I) 2019, la Guía 2019 para preparar el examen de selección para ingresar a la educación media superior (UNAM) y la Guía interactiva del concurso de asignación a la Educación Media Superior de la Zona Metropolitana de la Ciudad de México (COMIPEMS) 2019. El nivel de complejidad de las preguntas fue analizado de acuerdo con la Taxonomía de los objetivos de la educación. (Bloom, 1975). Con base en los resultados se ha identificado que existe una gran discordancia entre el nivel de los aprendizajes esperados sobre evolución biológica y los reactivos formulados para evaluarlos en el examen único de admisión a nivel medio superior en México.

Wandering the aisles of my local Woolworths in April this year, I noticed a large number of chocolate bilbies replacing chocolate rabbits. In these harsh economic times it seems that even the Easter bunny is in danger of losing his Easter job. While the changing shape of Easter chocolate may seem to be a harmless affair, the expulsion of the rabbit from Easter celebrations has a darker side. In this paper I look at the campaign to replace the Easter bunny with the Easter bilby, and the implications this mediated conservation move has for living rabbits in the Australian ecosystem. Essential to this discussion is the premise that studies of ecology must take into account the impact of media and culture on environmental issues. Of particular interest is the role of narrative, and the way the stories we tell about rabbits determine how they are treated in real life. While I recognise that the Australian bilby’s struggle for survival is a tale which should be told, I also argue that the vilification of the European-Australian rabbit is part of the native/invasive dualism which has ceased to be helpful, and has instead become a motivator of unproductive violence. In place of this simplified dichotomous narrative, I propose an ethic of "ecological remembrance" to combat the totalising eradication of the European rabbit from the Australian environment and culture. The Bilby vs the Bunny: A Case Study in "Media Selection" Easter Bunny says, ‘Bilby, I want you to have my job.You know about sharing and taking care.I think Australia should have an Easter Bilby.We rabbits have become too greedy and careless.Rabbits must learn from bilbies and other bush creatures’. The lines above are taken from Ali Garnett and Kaye Kessing’s children’s story, Easter Bilby, co-published by the Australian Anti-Rabbit Research Foundation as part of the campaign to replace the Easter bunny with the eco-politically correct Easter bilby. The first chocolate bilbies were made in 1982, but the concept really took off when major chocolate retailer Darrell Lea became involved in 2002. Since this time Haigh’s chocolate, Cadbury, and Pink Lady have also released delicious cocoa natives for consumption, and both Darrell Lea and Haigh’s use their profits to support bilby assistance programs, creating the “pleasant Easter sensation” that “eating a chocolate bilby is helping save the real thing” (Phillips). The Easter bilby campaign is a highly mediated approach to conservation which demonstrates the new biological principle Phil Bagust has recognised as “media selection.” Bagust observes that in our “hybridised global society” it is impossible to separate “the world of genetic selection from the world of human symbolic and material diversity as if they exist in different universes” (8). The Australian rabbit thrives in “natural selection,” having adapted to the Australian environment so successfully it threatens native species and the economic productivity of farmers. But the rabbit loses out in “cultural selection” where it is vilified in the media for its role in environmental degradation. The campaign to conserve the bilby depends, in a large part, on the rabbit’s failures in “media selection”. On Good Friday 2012 Sky News Australia quoted Mike Drinkwater of Wild Life Sydney’s support of the Easter bilby campaign: Look, the reason that we want to highlight the bilby as an iconic Easter animal is, number one, rabbits are a pest in Australia. Secondly, the bilby has these lovely endearing rabbit-like qualities. And thirdly, the bilby is a beautiful, iconic, native animal that is struggling. It is endangered so it’s important that we do all we can to support that. Drinkwater’s appeal to the bilby’s “endearing rabbit-like qualities” demonstrates that it is not the Australian rabbit’s individual embodiment which detracts from its charisma in Australian society. In this paper I will argue that the stories we tell about the European-Australian rabbit’s alienation from Indigenous country diminish the species cultural appeal. These stories are told with passionate conviction to save and protect native flora and fauna, but, too often, this promotion of the native relies on the devaluation of non-native life, to the point where individual rabbits are no longer morally considerable. Such a hierarchical approach to conservation is not only ethically problematic, but can also be ineffective because the native/invasive approach to ecology is overly simplistic. A History of Rabbit Stories In the Easter Bilby children’s book the illustrated rabbit offers to make itself disappear from the “Easter job.” The reason for this act of self-destruction is a despairing recognition of its “greedy and careless” nature, and at the same time, its selfless offer to be replaced by the ecologically conscious Bilby. In this sacrificial gesture is the implicit offering of all rabbit life for the salvation of native ecosystems and animal life. This plot line slots into a much larger series of stories we have been telling about the Australian environment. Libby Robin has observed that settler Australians have always had a love-hate relationship with the native flora and fauna of the continent (6), either devaluing native plants, animals, and ecosystems, or launching into an “overcompensating patriotic strut about the Australian biota” (Robin 9). The colonising dynamic of early Australian society was built on the devaluation of animals such as the bilby. This was reflected in the introduction of feral animals by “acclimatisation societies” and the privileging of “pets” such as cats and dogs over native animals (Plumwood). Alfred Crosby has made the persuasive argument that the invasion of Australia, and other “neo-European” countries, was, necessarily, more-than-human. In his work, Ecological Imperialism, Crosby charts the historical partnership between human European colonisers in Indigenous lands and the “grunting, lowing, neighing, crowing, chirping, snarling, buzzing, self-replicating and world-altering avalanche” (194) of introduced life that they brought with them. In response to this “guilt by association” Australians have reversed the values in the dichotomous colonial dynamic to devalue the introduced and so “empower” the colonised native. In this new “anti-colonial” story, rabbits signify a wound of colonisation which has spread across and infected indigenous country. J. M. Arthur’s (130) analysis of language in relation to colonisation highlights some of the important lexical characteristics in the rabbit stories we now tell. He observes that the rabbits’ impact on the county is described using a vocabulary of contamination: “It is a ‘menace’, a ‘problem’, an ‘infestation’, a ‘nuisance’, a ‘plague’” (170). This narrative of disease encourages a redemptive violence against living rabbits to “cure” the rabbit problem in order to atone for human mistakes in a colonial past. Redemptive Violence in Action Rabbits in Australia have been subject to a wide range of eradication measures over the past century including shooting, the destruction of burrows, poisoning, ferreting, trapping, and the well-known rabbit proof fence in Western Australia. Particularly noteworthy in this slaughter has been the introduction of biological control measures with the release of the savage and painful disease Myxomatosis in late December 1950, followed by the release of the Calicivirus (Rabbit Haemorrhage Disease, or RHD) in 1996. As recently as March 2012 the New South Wales Department of Primary Industries announced a 1.5 million dollar program called “RHD Boost” which is attempting to develop a more effective biological control agent for rabbits who have become immune to the Calicivirus. In this perverse narrative, disease becomes a cure for the rabbit’s contamination of Australian environments. Calicivirus is highly infectious, spreads rapidly, and kills rabbits en masse. Following the release of Calicivirus in 1995 it killed 10 million rabbits in eight weeks (Ponsonby Veterinary Centre). While Calicivirus appears to be more humane than the earlier biological control, Myxomatosis, there are indications that it causes rabbits pain and stress. Victims are described as becoming very quiet, refusing to eat, straining for breath, losing coordination, becoming feverish, and excreting bloody nasal discharge (Heishman, 2011). Post-mortem dissection generally reveals a “pale and mottled liver, many small streaks or blotches on the lungs and an enlarged spleen... small thrombi or blood clots” (Coman 173). Public criticism of the cruel methods involved in killing rabbits is often assuaged with appeals to the greater good of the ecosystem. The Anti-Rabbit research foundation state on their Website, Rabbit-Free Australia, that: though killing rabbits may sound inhumane, wild rabbits are affecting the survival of native Australian plants and animals. It is our responsibility to control them. We brought the European rabbit here in the first place — they are an invasive pest. This assumption of personal and communal responsibility for the rabbit “problem” has a fundamental blind-spot. Arthur (130) observes that the progress of rabbits across the continent is often described as though they form a coordinated army: The rabbit extends its ‘dominion’, ‘dispossesses’ the indigenous bilby, causes sheep runs to be ‘abandoned’ and country ‘forfeited’, leaving the land in ‘ecological tatters’. While this language of battle pervades rabbit stories, humans rarely refer to themselves as invaders into Aboriginal lands. Arthur notes that, by taking responsibility for the rabbit’s introduction and eradication, the coloniser assumes an indigenous status as they defend the country against the exotic invader (134). The apprehension of moral responsibility can, in this sense, be understood as the assumption of settler indigeneity. This does not negate the fact that assuming human responsibility for the native environment can be an act of genuine care. In a country scarred by a history of ecocide, movements like the Easter Bilby campaign seek to rectify the negligent mistakes of the past. The problem is that reactive responses to the colonial devaluation of native life can be unproductive because they preserve the basic structure of the native/invasive dichotomy by simplistically reversing its values, and fail to respond to more complex ecological contexts and requirements (Plumwood). This is also socially problematic because the native/invasive divide of nonhuman life overlays more complex human politics of colonisation in Australia. The Native/Invasive Dualism The bilby is currently listed as an “endangered” species in Queensland and as “vulnerable” nationally. Bilbies once inhabited 70% of the Australian landscape, but now inhabit less than 15% of the country (Save the Bilby Fund). This dramatic reduction in bilby numbers has multiple causes, but the European rabbit has played a significant role in threatening the bilby species by competing for burrows and food. Other threats come from the predation of introduced species, such as feral cats and foxes, and the impact of farmed introduced species, such as sheep and cattle, which also destroy bilby habitats. Because the rabbit directly competes with the bilby for food and shelter in the Australian environment, the bilby can be classed as the underdog native, appealing to that larger Australian story about “the fair go”. It seems that the Easter bilby campaign is intended to level out the threat posed by the highly successful and adaptive rabbit through promoting the bilby in the “cultural selection” stakes. This involves encouraging bilby-love, while actively discouraging love and care for the introduced rabbits which threaten the bilby’s survival. On the Rabbit Free Australia Website, the campaign rationale to replace the Easter bunny with the Easter bilby claims that: Very young children are indoctrinated with the concept that bunnies are nice soft fluffy creatures whereas in reality they are Australia’s greatest environmental feral pest and cause enormous damage to the arid zone. In this statement the lived corporeal presence of individual rabbits is denied as the “soft, fluffy” body disappears behind the environmentally problematic species’ behaviour. The assertion that children are “indoctrinated” to find rabbits love-able, and that this conflicts with the “reality” of the rabbit as environmentally destructive, denies the complexity of the living animal and the multiple possible responses to it. That children find rabbits “fluffy” is not the result of pro-rabbit propaganda, but because rabbits are fluffy! That Rabbit Free Australia could construe this to be some kind of elaborate falsehood demonstrates the disappearance of the individual rabbit in the native/invasive tale of colonisation. Rabbit-Free Australia seeks to eradicate the animal not only from Australian ecosystems, but from the hearts and minds of children who are told to replace the rabbit with the more fitting native bilby. There is no acceptance here of the rabbit as a complex animal that evokes ambivalent responses, being both worthy of moral consideration, care and love, and also an introduced and environmentally destructive species. The native/invasive dualism is a subject of sustained critique in environmental philosophy because it depends on a disjunctive temporal division drawn at the point of European settlement—1788. Environmental philosopher Thom van Dooren points out that the divide between animals who belong and animals who should be eradicated is “fundamentally premised on the reification of a specific historical moment that ignores the changing and dynamic nature of ecologies” (11). Mark Davis et al. explain that the practical value of the native/invasive dichotomy in conservation programs is seriously diminished and in some cases is becoming counterproductive (153). They note that “classifying biota according to their adherence to cultural standards of belonging, citizenship, fair play and morality does not advance our understanding of ecology” (153). Instead, they promote a more inclusive approach to conservation which accepts non-native species as part of Australia’s “new nature” (Low). Recent research into wildlife conservation indicates a striking lack of evidence for the case that pest control protects native diversity (see Bergstromn et al., Davis et al., Ewel & Putz, Reddiex & Forsyth). The problematic justification of “killing for conservation” becomes untenable when conservation outcomes are fundamentally uncertain. The mass slaughter which rabbits have been subjected to in Australia has been enacted with the goal of fostering life. This pursuit of creation through destruction, of re-birth through violent death, enacts a disturbing twist where death comes to signal the presence of life. This means, perversely, that a rabbit’s dead body becomes a valuable sign of environmental health. Conservation researchers Ben Reddiex and David M. Forsyth observe that this leads to a situation where environmental managers are “more interested in estimating how many pests they killed rather than the status of biodiversity they claimed to be able to protect” (715). What Other Stories Can We Tell about the Rabbit? With an ecological narrative that is failing, producing damage and death instead of fostering love and life, we are left with the question—what other stories can we tell about the place of the European rabbit in the Australian environment? How can the meaning ecologies of media and culture work in harmony with an ecological consciousness that promotes compassion for nonhuman life? Ignoring the native/invasive distinction entirely is deeply problematic because it registers the ecological history of Australia as continuity, and fails to acknowledge the colonising impact of European settlement on the environment. At the same time, continually reinforcing that divide through pro-invasive or pro-native stories drastically simplifies complex and interconnected ecological systems. Instead of the unproductive native/invasive dualism, ecologists and philosophers alike are suggesting “reconciliatory” approaches to the inhabitants of our shared environments which emphasise ecology as relational rather than classificatory. Evolutionary ecologist Scott P. Carroll uses the term “conciliation biology” as an alternative to invasion biology which focuses on the eradication of invasive species. “Conciliation biology recognises that many non-native species are permanent, that outcomes of native-nonnative interactions will vary depending on the scale of assessment and the values assigned to the biotic system, and that many non-native species will perform positive functions in one or more contexts” (186). This hospitable approach aligns with what Michael Rosensweig has termed “reconciliation ecology”—the modification and diversification of anthropogenic habitats to harbour a wider variety of species (201). Professor of Ecology and Evolutionary Biology Mark Bekoff encourages a “compassionate conservation” which avoids the “numbers game” of species thinking where certain taxonomies are valued above others and promotes approaches which “respect all life; treat individuals with respect and dignity; and tread lightly when stepping into the lives of animals”(24). In a similar vein environmental philosopher Deborah Bird Rose offers the term “Eco-reconciliation”, to describe a mode of “living generously with others, singing up relationships so that we all flourish” (Wild Dog 59). It may be that the rabbit cannot live in harmony with the bilby, and in this situation I am unsure of what a conciliation approach to ecology might look like in terms of managing both of these competing species. But I am sure what it should not look like if we are to promote approaches to ecology and conservation which avoid the simplistic dualism of native/invasive. The devaluation of rabbit life to the point of moral inconsiderability is fundamentally unethical. By classifying certain lives as “inappropriate,” and therefore expendable, the process of rabbit slaughter is simply too easy. The idea that the rabbit should disappear is disturbing in its abstract approach to these living, sentient creatures who share with us both place and history. A dynamic understanding of ecology dissipates the notion of a whole or static “nature.” This means that there can be no simple or comprehensive directives for how humans should interact with their environments. One of the most insidious aspects of the native/invasive divide is the way it makes violent death appear inevitable, as though rabbits must be culled. This obscures the many complex and contingent choices which determine the fate of nonhuman life. Understanding the dynamism of ecology requires an acceptance that nature does not provide simple prescriptive responses to problems, and instead “people are forced to choose the kind of environment they want” (189) and then take actions to engender it. This involves difficult decisions, one of which is culling to maintain rabbit numbers and facilitate environmental resilience. Living within a world of “discordant harmonies”, as Daniel Botkin evocatively describes it, environmental decisions are necessarily complex. The entanglement of ecological systems demands that we reject simplistic dualisms which offer illusory absolution from the consequences of the difficult choices humans make about life, ecologies, and how to manage them. Ecological Remembrance The vision of a rabbit-free Australia is unrealistic. As organisation like the Anti-Rabbit Research Foundation pursue this future ideal, they eradicate rabbits from the present, and seek to remove them from the past by replacing them culturally with the more suitable bilby. Culled rabbits lie rotting en masse in fields, food for no one, and even their cultural impact in human society is sought to be annihilated and replaced with more appropriate native creatures. The rabbits’ deaths do not turn back to life in transformative and regenerative processes that are ecological and cultural, but rather that death becomes “an event with no future” (Rose, Wild Dog 25). This is true oblivion, as the rabbit is entirely removed from the world. In this paper I have made a case for the importance of stories in ecology. I have argued that the kinds of stories we tell about rabbits determines how we treat them, and so have positioned stories as an essential part of an ecological system which takes “cultural selection” seriously. In keeping with this emphasis on story I offer to the conciliation push in ecological thinking the term “ecological remembrance” to capture an ethic of sharing time while sharing space. This spatio-temporal hospitality is focused on maintaining heterogeneous memories and histories of all beings who have impacted on the environment. In Deborah Bird Rose’s terms this is a “recuperative work” which commits to direct dialogical engagement with the past that is embedded in the present (Wild Country 23). In this sense it is a form of recuperation that promotes temporal and ecological continuity. Eco-remembrance aligns with dynamic understandings of ecology because it is counter-linear. Instead of approaching the past as a static idyll, preserved and archived, ecological remembrance celebrates the past as an ongoing, affective presence which is lived and performed. Ecological remembrance, applied to the European rabbit in Australia, would involve rejecting attempts to extricate the rabbit from Australian environments and cultures. It would seek acceptance of the rabbit as part of Australia’s “new nature” (Low), and aim for recognition of the rabbit’s impact on human society as part of dynamic multi-species ecologies. In this sense ecological remembrance of the rabbit directly opposes the goal of the Foundation for Rabbit Free Australia to eradicate the European rabbit from Australian environment and culture. On the Rabbit Free Australia website, the section on biological controls states that “the point is not how many rabbits are killed, but how many are left behind”. The implication is that the millions upon millions of rabbit lives extinguished have vanished from the earth, and need not be remembered or considered. However, as Deborah Rose argues, “all deaths matter” (Wild Dog 21) and “no death is a mere death” (Wild Dog 22). Every single rabbit is an individual being with its own unique life. To deny this is tantamount to claiming that each rabbit that dies from shooting or poisoning is the same rabbit dying again and again. Rose has written that “death makes claims upon all of us” (Wild Dog 19). These are claims of ethics and compassion, a claim that “we look into the eyes of the dying and not flinch, that we reach out to hold and to help” (Wild Dog 20). This claim is a duty of remembrance, a duty to “bear witness” (Wiesel 160) to life and death. The Nobel Peace Prize winning author, Elie Wiesel, argued that memory is a reconciliatory force that creates bonds as mass annihilation seeks to destroy them. Memory ensures that no life becomes truly life-less as it wrests the victims of mass slaughter from “oblivion” and allows the dead to “vanquish death” (21). In a continent inhabited by dead rabbits—a community of the dead—remembering these lost individuals and their lost lives is an important task for making sure that no death is a mere death. An ethic of ecological remembrance follows this recuperative aim. References Arthur, Jay M. The Default Country: A Lexical Cartography of Twentieth-Century Australia. Sydney: UNSW Press, 2003. Bagust, Phil. “Cuddly Koalas, Beautiful Brumbies, Exotic Olives: Fighting for Media Selection in the Attention Economy.” “Imaging Natures”: University of Tasmania Conference Proceedings (2004). 25 April 2012 ‹www.utas.edu.au/arts/imaging/bagust.pdf› Bekoff, Marc. “First Do No Harm.” New Scientist (28 August 2010): 24 – 25. Bergstrom, Dana M., Arko Lucieer, Kate Kiefer, Jane Wasley, Lee Belbin, Tore K. Pederson, and Steven L. Chown. “Indirect Effects of Invasive Species Removal Devastate World Heritage Island.” Journal of Applied Ecology 46 (2009): 73– 81. Botkin, Daniel. B. Discordant Harmonies: A New Ecology for the Twenty-first Century. New York & Oxford: Oxford University Press, 1990. Carroll, Scott. P. “Conciliation Biology: The Eco-Evolutionary Management of Permanently Invaded Biotic Systems.” Evolutionary Applications 4.2 (2011): 184 – 99. Coman, Brian. Tooth and Nail: The Story of the Rabbit in Australia. Melbourne: The Text Publishing Company, 1999. Crosby, Alfred W. Ecological Imperialism: The Biological Expansion of Europe, 900 – 1900. Second Edition. Cambridge: Cambridge University Press, 2004. Davis, Mark., Matthew Chew, Richard Hobbs, Ariel Lugo, John Ewel, Geerat Vermeij, James Brown, Michael Rosenzweig, Mark Gardener, Scott Carroll, Ken Thompson, Steward Pickett, Juliet Stromberg, Peter Del Tredici, Katharine Suding, Joan Ehrenfield, J. Philip Grime, Joseph Mascaro and John Briggs. “Don’t Judge Species on their Origins.” Nature 474 (2011): 152 – 54. Ewel, John J. and Francis E. Putz. “A Place for Alien Species in Ecosystem Restoration.” Frontiers in Ecology and the Environment 2.7 (2004): 354-60. Forsyth, David M. and Ben Reddiex. “Control of Pest Mammals for Biodiversity Protection in Australia.” Wildlife Research 33 (2006): 711–17. Garnett, Ali, and Kaye Kessing. Easter Bilby. Department of Environment and Heritage: Kaye Kessing Productions, 2006. Heishman, Darice. “VHD Factsheet.” House Rabbit Network (2011). 15 June 2012 ‹http://www.rabbitnetwork.org/articles/vhd.shtml› Low, Tim. New Nature: Winners and Losers in Wild Australia. Melbourne: Penguin, 2002. Phillips, Sara. “How Eating Easter Chocolate Can Save Endangered Animals.” ABC Environment (1 April 2010). 15 June 2011 ‹http://www.abc.net.au/environment/articles/2010/04/01/2862039.htm› Plumwood, Val. “Decolonising Australian Gardens: Gardening and the Ethics of Place.” Australian Humanities Review 36 (2005). 15 June 2012 ‹http://www.australianhumanitiesreview.org/archive/Issue-July-2005/09Plumwood.html› Ponsonby Veterinary Centre. “Rabbit Viral Hemorrhagic Disease (VHD).” Small Pets. 26 May 2012 ‹http://www.petvet.co.nz/small_pets.cfm?content_id=85› Robin, Libby. How a Continent Created a Nation. Sydney: UNSW Press, 2007. Rose, Deborah Bird. Reports From a Wild Country: Ethics for Decolonisation. Sydney: University of New South Wales Press, 2004. ——-. Wild Dog Dreaming: Love and Extinction. Charlottesville and London: University of Virginia Press, 2011. Rosenzweig, Michael. L. “Reconciliation Ecology and the Future of Species Diversity.” Oryx 37.2 (2003): 194 – 205. Save the Bilby Fund. “Bilby Fact Sheet.” Easterbilby.com.au (2003). 26 May 2012 ‹http://www.easterbilby.com.au/Project_material/factsheet.asp› Van Dooren, Thom. “Invasive Species in Penguin Worlds: An Ethical Taxonomy of Killing for Conservation.” Conservation and Society 9.4 (2011): 286 – 98. Wiesel, Elie. From the Kingdom of Memory. New York: Summit Books, 1990.

Photo ID 72893750 © Rawpixelimages|Dreamstime.com ABSTRACT Solidarity is a concept increasingly employed in bioethics whose application merits further clarity and explanation. Given how vital cooperation and community-level care are to mitigating communicable disease transmission, we use lessons from the COVID-19 pandemic to reveal how solidarity is a useful descriptive and analytical tool for public health scholars, practitioners, and policymakers. Drawing upon an influential framework of solidarity that highlights how solidarity arises from the ground up, we reveal how structural forces can impact the cultivation of solidarity from the top down, particularly through ensuring robust access to important social determinants of health. Public health institutions can support solidarity movements among individuals and communities by adopting a lens of social justice when considering public health priorities and, in turn, promote health equity. INTRODUCTION Over the past two decades, scholars have invoked the concept of solidarity when assessing a wide range of topics in bioethics, from CRISPR-Cas9 technology to organ donation to structural racism.[1] However, the growing literature on solidarity has not fully examined the roles and responsibilities of institutions and governments in fostering solidarity, especially regarding public health measures that implicate entire populations. We argue that it remains unclear how public health institutions should engage with solidarity and how their engagement will affect public health and its ethics. We first take Prainsack and Buyx’ three-tiered framework as an analytical starting point.[2] We then explore how public health institutions can foster solidarity by carefully considering factors that may bolster it on an interpersonal, community, and national scale. We conclude that public health institutions should adopt a lens of social justice to promote solidarity at the interpersonal and community levels, thereby promoting equity in future public health efforts. BACKGROUND Calls for solidarity in bioethics raise longstanding normative questions about the nature and limits of our duties to one another and how to weigh autonomy over considerations of justice.[3] Though the term is diversely applied, Prainsack and Buyx propose a potentially unifying definition in the 2011 Nuffield Council report, “Solidarity: Reflections On An Emerging Concept in Bioethics.” The report defines solidarity as an activity involving “shared practices reflecting a collective commitment to carry financial, social, emotional, and or other ‘costs’ to assist others.” Their conceptualization also includes important features that distinguish solidarity from other values like empathy or altruism: solidarity emphasizes action rather than mere internal feeling and recognition of connection as motivation.[4] Bioethicists have since applied this conceptualization when analyzing issues in public and global health, given that population-level efforts need cooperation from individuals and communities. Prainsack and Buyx further note that solidarity is relevant in bioethics discourses about justice and equity, in support of providing aid to low- and middle-income countries, and as a value exemplified by European welfare states.[5] Other bioethicists have argued that promoting solidarity can contribute to community engagement, partnership with Tribal communities, and global health equity.[6] Most recently, scholars have applied solidarity as a lens to assess the COVID-19 pandemic, highlighting the pitfalls of national mitigation efforts and global disparities in disease outcomes.[7] I. Solidarity at Three Levels It seems impossible to foster solidarity in public health if we cannot identify it in general contexts. Prainsack and Buyx articulate three levels of solidarity: interpersonal solidarity, group solidarity, and legal or contractual codifications of solidarity.[8] They argue that each level inherently informs the one ‘above’ it in a unilateral direction. In other words, solidarity is fundamentally a bottom-up phenomenon. Solidarity among individuals influences group norms, which then have the potential to shape policy and institutional practice.[9] Within the Prainsack and Buyx framework, it would seem nonsensical to posit how solidarity might be expressed vertically or from the “top down.” It appears intuitively odd to imagine how a government entity might ‘be’ in solidarity with a person or group if solidarity requires some cognition about their condition per Prainsack and Buyx’ definition. Some have argued that solidarity does not seem like something that one can impose, as instances of it arise from agents recognizing and acting upon some bond rather than in response to a command. Indeed, people may be rightfully hesitant to engage in solidarity if the official messaging is overly paternalistic or coercive.[10] However, some authors have countered that governments can express solidarity through enacting structural and policy changes, though it is ambiguous how these actions are distinct from a justice-driven approach.[11] If a bottom-up approach is thus the most practical means of achieving policy that reflects solidarity, then it does not add much to public health. Institutions would be ineffective without the population’s initiation of the corresponding social norms. However, we find this conclusion overly pessimistic. Fostering a culture of solidarity to improve public health has potential merit. Prainsack and Buyx’ framework overlooks how public health actors can influence solidarity between individuals and across communities. To clarify, we agree with the view that solidarity is a bottom-up phenomenon. Solidarity may not be able to originate in a top-down fashion, but we suggest that public health institutions can take a more active role in providing the public with accurate information, promoting social justice, and intervening in the social determinants of health. II. The COVID-19 Pandemic as a Case Study Lessons learned from the ongoing COVID-19 pandemic support our argument. The pandemic deepened socioeconomic disparities in the US and hindered access to vital resources such as food, housing, and healthcare.[12] Prainsack recently noted: “[n]ext to the immediate health effects of the virus, poverty and grave inequalities have been the root causes of human suffering during the pandemic.”[13] Prior to the pandemic, many rural and low-income populations lacked reliable access to the internet and devices like laptops or smartphones. This continued lack of access restricts the flow of information and prevents people from accessing telemedicine services.[14] Preexisting social, political, and health inequities worsened health outcomes among many marginalized racial and ethnic groups. It is well-documented that communities of color, including Black, American Indian or Alaska Native, and Latinx populations, had greater COVID-related mortality and morbidity due to the effects of structural racism.[15] Although federal US agencies such as the Centers for Disease Control and Prevention enacted laws that provided safety nets (e.g., the Federal Eviction Moratorium), the majority of such programs have ended, leaving many with little assistance and the threat of further hardship.[16] These disparities are relevant because Prainsack, Buyx, and others note that solidarity arises from agents recognizing and acting on some perceived attainable collective goal(s). Income inequality and disparate access to food, education, and health care may lead people to consider public health goals unattainable. This could limit the desire to work toward those goals collectively.[17] The existing literature on collective action theory supports this intuition. It emphasizes that structural conditions, such as an absence of perceived hope for social change among a group, can lead to low ‘group efficacy’ and little willingness to cooperate, both within and across socioeconomic strata.[18] The pandemic spurred countless messages from public health agencies. The messaging did not recognize or attend to the different material realities and circumstances of the US population. How can people feel comfortable getting vaccinated if they deeply distrust the government, including public health institutions? How can people remain motivated to wear masks and distance themselves if they cannot afford basic necessities and work jobs without adequate pay and leave policies? We ask these questions to illustrate how socioeconomic disparities can marginalize people if they feel ignored, apathetic, or resentful of those better off or those in power whom they perceive to “not be doing enough.” This marginalization precludes the formation of solidarity. There are instances when a population has disparate access to resources and social capital, but solidarity may still emerge from a shared goal or vision for the future. For example, a heterogeneous population living in the same town may come together to protest an environmental injustice that impacts their water supply with the common goal of securing access to safe drinking water. However, many populations in the US failed to recognize shared goals of this kind during the COVID-19 pandemic. A significant minority of the US population was reluctant to acknowledge the severity of COVID-19 infection and thus refused to participate in efforts to mitigate its spread. Even between groups who shared the goal of slowing COVID-19 transmission, the methods were widely debated. Approximately 20 percent of the adult population eligible for vaccination remains unvaccinated.[19] Governmental bodies responsible for disseminating information, coordinating the allocation of resources, and establishing guidelines have a large role in mediating these disagreements and intervening in socioeconomic conditions that impact people's ability and willingness to engage in solidarity. III. Solidarity, Social Justice, and the Role of Public Health Institutions Adopting a lens of social justice provides further insights into how public health actors impact solidarity. Powers and Faden argue that the “foundational moral justification for the social institution of public health is social justice.”[20] Their theory of social justice has two aims. First, it ensures that everyone has a sufficient amount of the six core elements of well-being and that public health institutions are responsible for “adopting policies and creating environments” where all can flourish.[21] Second, public health institutions should distribute resources meant to promote well-being and focus on the “needs of those who are the most disadvantaged.”[22] Public health institutions should enact policies that address injustice. In doing so, public health institutions can seed the opportunity to build solidarity from the bottom up. Equipping individuals and communities with resources will foster cooperation and adherence to policies that require solidarity, such as masking and vaccination. This is consistent with arguments illustrating how institutions such as Tribal governments promote the conditions needed for their group, and especially its most vulnerable members, to flourish.[23] Addressing social determinants of health with a social justice lens will create the circumstances under which more individuals and groups can find common causes and foster solidarity. In the long run, such efforts may result in the establishment of values and practices from the bottom up. There are societal and public health preconditions required before institutions can expect their audience to act in solidarity with one another. Through their great influence over information and resources, public institutions do have the power to impact what values are most widespread. Furthermore, public health may foster trust and hope, which are important psychosocial factors that influence collective action,[24] if policies increase access to resources that promote well-being. Messaging efficacy also depends on the context of public trust, education, and whether the institutions meet one’s basic needs. Disparate messaging across different public institutions may confuse or disillusion individuals. To apply our theory of solidarity to the decision to vaccinate, a policy would be to foster conditions that facilitate access to vaccines and information about vaccine efficacy instead of imposing a top-down mandate without first eliciting public trust. IV. Counterargument Some argue that discordant public health messaging, ineffective government, and inadequate social programs can also bring people together under pressure and foster solidarity. One may argue that the most powerful motivators towards solidarity are strife and disparity, as evidenced throughout history. During the pandemic alone, political struggle and personal hardship inspired solidarity in the US, from individual neighbors helping each other to mutual aid groups forming across communities. We thus do not claim that solidarity is possible only when our government programs and public health institutions are most effective. We instead point out that solidarity can be further hindered when people feel alienated, hopeless, and pitted against each other. CONCLUSION Many competing conceptualizations of solidarity persist in the bioethics literature, and Prainsack and Buyx offer one compelling framework that public health ethicists continue to draw upon.[25] However, their framework fails to acknowledge how public health institutions impact interpersonal and group solidarity. Public health institutions can foster solidarity through actions other than mere messaging, invoking catchphrases like “we are all in this together.” Efforts to address socioeconomic preconditions and alleviate health disparities can cultivate group solidarity. As we saw during the pandemic, cooperation and solidarity go hand-in-hand with disease mitigation efforts; solidarity has clear intrinsic value.[26] As this relationship becomes more apparent, we will continue to see attempts from public health institutions to foster or invoke solidarity. Therefore, public health institutions would be remiss to ignore their role in addressing the social determinants of health. Adopting a social justice lens when planning public health interventions will clarify and strengthen their role in facilitating solidarity. Ultimately, if health disparities continue to persist or widen, it is very hard to imagine how group solidarity can ever be achieved. The widescale adoption of many public health measures needed to promote health and well-being would be conducive to solidarity. - Disclaimer: The opinions expressed are the authors’ and do not represent the views of the NIH, DHHS, or the U.S. government. Funding Disclosure: This work was supported in part by the Intramural Program of the National Institutes of Health Clinical Center. - [1] John J Mulvihill et al., “Ethical Issues of CRISPR Technology and Gene Editing through the Lens of Solidarity,” British Medical Bulletin 122 (2017): 17–29, https://doi.org/10.1093/bmb/ldx002; Ben Saunders, “Altruism or Solidarity? The Motives for Organ Donation and Two Proposals,” Bioethics 26, no. 7 (September 2012): 376–81, https://doi.org/10.1111/j.1467-8519.2012.01989.x; -Vanessa Y Hiratsuka, “SPECIAL REPORT: A Critical Moment in Bioethics: Reckoning with Anti-Black Racism through Intergenerational Dialogue A Call for Solidarity in Bioethics: Confronting Anti-Black Racism Together,” 2022, https://doi.org/10.1002/hast.1380. [2] Prainsack and Buyx, Solidarity: Reflections on an Emerging Concept in Bioethics London: Nuffield Council on Bioethics, 2011; Prainsack and Buyx, “Solidarity in Contemporary Bioethics--towards a New Approach.” Bioethics 26, no. 7 (September 2012): 343–50. https://doi.org/10.1111/J.1467-8519.2012.01987.X. [3] Bob Simpson, “A ‘We’ Problem for Bioethics and the Social Sciences: A Response to Barbara Prainsack,” Science, Technology, & Human Values 43, no. 1 (January 12, 2018): 45–55, https://doi.org/10.1177/0162243917735899. [4] Barbara Prainsack and Alena Buyx, Solidarity: Reflections on an Emerging Concept in Bioethics (London: Nuffield Council on Bioethics, 2011). [5] Barbara Prainsack and Alena Buyx, “Solidarity in Contemporary Bioethics--towards a New Approach,” Bioethics 26, no. 7 (September 2012): 343–50, https://doi.org/10.1111/J.1467-8519.2012.01987.X. [6] Bridget Pratt, Phaik Yeong Cheah, and Vicki Marsh, “Solidarity and Community Engagement in Global Health Research,” The American Journal of Bioethics : AJOB 20, no. 5 (May 3, 2020): 43–56, https://doi.org/10.1080/15265161.2020.1745930; Sara Chandros Hull, F. Leah Nez (Diné), and Juliana M. Blome, “Solidarity as an Aspirational Basis for Partnership with Tribal Communities,” The American Journal of Bioethics 21, no. 10 (October 3, 2021): 14–17, https://doi.org/10.1080/15265161.2021.1965258; Mbih J. Tosam et al., “Global Health Inequalities and the Need for Solidarity: A View from the Global South,” Developing World Bioethics 18, no. 3 (September 1, 2018): 241–49, https://doi.org/10.1111/DEWB.12182. [7] Peter West-Oram, “Solidarity Is for Other People: Identifying Derelictions of Solidarity in Responses to COVID-19,” Journal of Medical Ethics 47, no. 2 (February 1, 2021): 65–68, https://doi.org/10.1136/MEDETHICS-2020-106522; Barbara Prainsack, “Solidarity in Times of Pandemics,” Democratic Theory 7, no. 2 (December 1, 2020): 124–33, https://doi.org/10.3167/DT.2020.070215; F. Marijn Stok et al., “Social Inequality and Solidarity in Times of COVID-19,” International Journal of Environmental Research and Public Health 18, no. 12 (June 2, 2021), https://doi.org/10.3390/IJERPH18126339; Ming Jui Yeh, “Solidarity in Pandemics, Mandatory Vaccination, and Public Health Ethics,” American Journal of Public Health 112, no. 2 (February 1, 2022): 255–61, https://doi.org/10.2105/AJPH.2021.306578; Barbara Prainsack, “Beyond Vaccination Mandates: Solidarity and Freedom During COVID-19.,” Am J Public Health 112, no. 2 (February 1, 2022): 232–33, https://doi.org/10.2105/AJPH.2021.306619. [8] Prainsack and Buyx, Solidarity: Reflections on an Emerging Concept in Bioethics London: Nuffield Council on Bioethics, 2011; Prainsack and Buyx, “Solidarity in Contemporary Bioethics--towards a New Approach.” Bioethics 26, no. 7 (September 2012): 343–50. https://doi.org/10.1111/J.1467-8519.2012.01987.X. [9] Prainsack and Buyx, Solidarity: Reflections on an Emerging Concept in Bioethics London: Nuffield Council on Bioethics, 2011; Prainsack and Buyx, “Solidarity in Contemporary Bioethics--towards a New Approach.” Bioethics 26, no. 7 (September 2012): 343–50. https://doi.org/10.1111/J.1467-8519.2012.01987.X. [10] Yeh, “Solidarity in Pandemics, Mandatory Vaccination, and Public Health Ethics”; Prainsack, “Beyond Vaccination Mandates: Solidarity and Freedom During COVID-19.” [11] Ho, Anita, and Iulia Dascalu. "Relational solidarity and COVID-19: an ethical approach to disrupt the global health disparity pathway." Global Bioethics 32, no. 1 (2021): 34-50; West-Oram, Peter. "Solidarity is for other people: identifying derelictions of solidarity in responses to COVID-19." Journal of Medical Ethics 47, no. 2 (2021): 65-68. [12] Monica Webb Hooper, Anna María Nápoles, and Eliseo J. Pérez-Stable, “COVID-19 and Racial/Ethnic Disparities,” JAMA 323, no. 24 (June 23, 2020): 2466, https://doi.org/10.1001/jama.2020.8598. [13] Prainsack, Barbara. “Beyond Vaccination Mandates: Solidarity and Freedom During COVID-19.” Am J Public Health 112, no. 2 (February 1, 2022): 232–33. https://doi.org/10.2105/AJPH.2021.306619. [14] Camille A Clare, “Telehealth and the Digital Divide as a Social Determinant of Health during the COVID-19 Pandemic,” Network Modeling Analysis in Health Informatics and Bioinformatics 10 (2021): 26, https://doi.org/10.1007/s13721-021-00300-y. [15] Patrick Nana-Sinkam et al., “Health Disparities and Equity in the Era of COVID-19,” Journal of Clinical and Translational Science 5, no. 1 (March 16, 2021): e99, https://doi.org/10.1017/cts.2021.23. [16] Kathryn M Leifheit et al., “Expiring Eviction Moratoriums and COVID-19 Incidence and Mortality,” American Journal of Epidemiology 190, no. 12 (December 1, 2021): 2503–10, https://doi.org/10.1093/aje/kwab196. [17] Barbara Prainsack, “Solidarity in Times of Pandemics,” Democratic Theory 7, no. 2 (December 1, 2020): 124–33, https://doi.org/10.3167/DT.2020.070215 [18] Maximilian Agostini and Martijn van Zomeren, “Toward a Comprehensive and Potentially Cross-Cultural Model of Why People Engage in Collective Action: A Quantitative Research Synthesis of Four Motivations and Structural Constraints.,” Psychological Bulletin 147, no. 7 (July 2021): 667–700, https://doi.org/10.1037/bul0000256. [19] Department of Health and Human Services (HHS) Centers for Disease Control and Prevention (HHS/CDC), “COVID Data Tracker,” 2023, https://covid.cdc.gov/covid-data-tracker. [20] Powers, Madison, and Ruth Faden. Social Justice: The Moral Foundation of Public Health and Health Policy. 1st editio. New York: Oxford Press, 2006, p. 9 and Chapter 4 [21] Powers and Faden, Social Justice: The Moral Foundation of Public Health and Health Policy; Madison Powers and Ruth Faden, Structural Injustice: Power, Advantage, and Human Rights (New York: Oxford University Press, 2019). [22] Powers, Madison, and Ruth Faden. Social Justice: The Moral Foundation of Public Health and Health Policy. 1st editio. New York: Oxford Press, 2006, p. 10 [23] Bobby Saunkeah et al., “Extending Research Protections to Tribal Communities,” The American Journal of Bioethics 21, no. 10 (October 3, 2021): 5–12, https://doi.org/10.1080/15265161.2020.1865477. [24] Agostini and van Zomeren, “Toward a Comprehensive and Potentially Cross-Cultural Model of Why People Engage in Collective Action: A Quantitative Research Synthesis of Four Motivations and Structural Constraints.” [25] Prainsack and Buyx, Solidarity: Reflections on an Emerging Concept in Bioethics. [26] Ruth Chadwick, “COVID‐19 and the Possibility of Solidarity,” Bioethics 34, no. 7 (September 8, 2020): 637–637, https://doi.org/10.1111/bioe.12813.