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2. A twin analysis to estimate genetic and environmental factors contributing to variation in weighted gene co-expression network module eigengenes.

Author

Gillespie, Nathan, Bell, Tyler, Hearn, Gentry, Hess, Jonathan, Tsuang, Ming, Lyons, Michael, Franz, Carol, Kremen, William, and Glatt, Stephen

Subjects
heritability, module eigengenes, weighted gene co‐expression network analysis, Humans, Male, Gene Regulatory Networks, Aged, Gene-Environment Interaction, Middle Aged, Twins, Genetic Variation, Gene Expression Profiling, Twins, Monozygotic, Phenotype
Abstract

Multivariate network-based analytic methods such as weighted gene co-expression network analysis are frequently applied to human and animal gene-expression data to estimate the first principal component of a module, or module eigengene (ME). MEs are interpreted as multivariate summaries of correlated gene-expression patterns and network connectivity across genes within a module. As such, they have the potential to elucidate the mechanisms by which molecular genomic variation contributes to individual differences in complex traits. Although increasingly used to test for associations between modules and complex traits, the genetic and environmental etiology of MEs has not been empirically established. It is unclear if, and to what degree, individual differences in blood-derived MEs reflect random variation versus familial aggregation arising from heritable or shared environmental influences. We used biometrical genetic analyses to estimate the contribution of genetic and environmental influences on MEs derived from blood lymphocytes collected on a sample of N = 661 older male twins from the Vietnam Era Twin Study of Aging (VETSA) whose mean age at assessment was 67.7 years (SD = 2.6 years, range = 62-74 years). Of the 26 detected MEs, 14 (56%) had statistically significant additive genetic variation with an average heritability of 44% (SD = 0.08, range = 35%-64%). Despite the relatively small sample size, this demonstration of significant family aggregation including estimates of heritability in 14 of the 26 MEs suggests that blood-based MEs are reliable and merit further exploration in terms of their associations with complex traits and diseases.

Published
2025

3. Exploring Geographic Variation in Equitable Postsecondary Value among U.S. Community Colleges. Final Report

Author

American Institutes for Research (AIR), Roman Ruiz, and Adam Hearn

Abstract

The Institute for Higher Education Policy's (IHEP) Equitable Value Explorer (EVE) data tool provides measures of economic value based on students' post-college earnings relative to the state in which their postsecondary institution is located. Such a broad geographic unit, however, may lead to inadequate comparisons for institutions like community colleges that primarily serve students who live and work within their immediate area. This study uses data from IHEP's EVE data tool and builds on the Postsecondary Value Framework (PVF) by redefining economic value thresholds based on the core-based statistical area (CBSA) in which an institution is located. CBSAs are federally defined geographic units that reflect a "core area containing a substantial population nucleus, together with adjacent communities having a high degree of economic and social integration" irrespective of state borders (U.S. Census Bureau, 2021). By examining postsecondary value across CBSAs, this study acknowledges that earnings outcomes vary dramatically by place, which are not necessarily bounded by state borders. For example, 61 of the 939 defined CBSAs include more than one state, with the Philadelphia-Camden-Wilmington CBSA and the Washington-Arlington-Alexandria CBSA each including portions of four states or jurisdictions. This study focuses on community colleges, which typically enroll individuals who live nearby (Jepsen & Montgomery, 2009) and produce graduates with less-than-4-year degrees who are less geographically mobile (Malamud & Wozniak, 2012). By focusing on this institutional sector, we can isolate the relationship more directly between postsecondary enrollment and earnings by reducing the likelihood that earnings are attributable to geographic mobility into and after college. In addition, this study extends the EVE data tool by moving beyond calculating measures of economic value to investigating the institution-level and community-level characteristics associated with positive (and negative) value.

Published
2024

4. Exploring Geographic Variation in Equitable Postsecondary Value among U.S. Community Colleges. Executive Summary

Author

American Institutes for Research (AIR), Roman Ruiz, and Adam Hearn

Abstract

Community colleges serve many critical purposes for residents within their local service areas by providing relatively low-cost (Ma & Pender, 2023), open-access postsecondary education and workforce-focused training (Jacobs & Worth, 2019). A recent national survey of previously enrolled community college students finds that "gaining skills to be successful in work" was the most frequently cited (74%) motivation for enrollment, yet only about half of career-motivated students reported meeting their work-related goals (e.g., financially support self and family, earn more money) after leaving their community college (Strada Education Foundation, 2023). In response to the public's questioning of the value of higher education, the Postsecondary Value Commission (2021) and its resulting Postsecondary Value Framework (PVF) have encouraged higher education researchers and data practitioners to quantify the value postsecondary institutions provide to students more explicitly. For example, the Institute for Higher Education Policy (IHEP) has used publicly available data to measure students' earnings against the PVF, using the resulting data to construct the Equitable Value Explorer (EVE), an interactive data tool. Given the hyperlocal enrollment of community college students and their primarily economic reasons for choosing to enroll in college, place-based measures of economic value are increasingly important to understand. AIR used publicly available federal data sources, including the Integrated Postsecondary Education Data System (IPEDS) and the American Community Survey (ACS), along with data from IHEP's EVE data tool to create a novel analytic data set that included institution-level and CBSA-level variables. Following the methodology advanced by the Postsecondary Value Commission, we calculated measures of economic value (dependent variable) for each community college in our analytic sample based on two value thresholds: the minimum economic return threshold, or T0, and the earnings premium threshold, or T1. We examined economic value using descriptive statistics (e.g., percent distribution) and through correlation and regression analyses.

Published
2024

5. Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C).

Author

Bellos, Evangelos, Santillo, Dilys, Vantourout, Pierre, Jackson, Heather, Duret, Amedine, Hearn, Henry, Seeleuthner, Yoann, Talouarn, Estelle, Hodeib, Stephanie, Patel, Harsita, Powell, Oliver, Yeoh, Sophya, Mustafa, Sobia, Habgood-Coote, Dominic, Nichols, Samuel, Estramiana Elorrieta, Leire, DSouza, Giselle, Wright, Victoria, Estrada-Rivadeneyra, Diego, Tremoulet, Adriana, Dummer, Kirsten, Netea, Stejara, Condino-Neto, Antonio, Lau, Yu, Núñez Cuadros, Esmeralda, Toubiana, Julie, Holanda Pena, Marisol, Rieux-Laucat, Frédéric, Luyt, Charles-Edouard, Haerynck, Filomeen, Mège, Jean, Chakravorty, Samya, Haddad, Elie, Morin, Marie-Paule, Metin Akcan, Özge, Keles, Sevgi, Emiroglu, Melike, Alkan, Gulsum, Tüter Öz, Sadiye, Elmas Bozdemir, Sefika, Morelle, Guillaume, Volokha, Alla, Kendir-Demirkol, Yasemin, Sözeri, Betul, Coskuner, Taner, Yahsi, Aysun, Gulhan, Belgin, Kanik-Yuksek, Saliha, Bayhan, Gulsum, Ozkaya-Parlakay, Aslinur, Yesilbas, Osman, Hatipoglu, Nevin, Ozcelik, Tayfun, Belot, Alexandre, Chopin, Emilie, Barlogis, Vincent, Sevketoglu, Esra, Menentoglu, Emin, Gayretli Aydin, Zeynep, Bloomfield, Marketa, AlKhater, Suzan, Cyrus, Cyril, Stepanovskiy, Yuriy, Bondarenko, Anastasiia, Öz, Fatma, Polat, Meltem, Fremuth, Jiří, Lebl, Jan, Geraldo, Amyrath, Jouanguy, Emmanuelle, Carter, Michael, Wellman, Paul, Peters, Mark, Pérez de Diego, Rebeca, Edwards, Lindsey, Chiu, Christopher, Noursadeghi, Mahdad, Bolze, Alexandre, Shimizu, Chisato, Kaforou, Myrsini, Hamilton, Melissa, Herberg, Jethro, Schmitt, Erica, Rodriguez-Palmero, Agusti, Pujol, Aurora, Kim, Jihoon, Cobat, Aurélie, Abel, Laurent, Zhang, Shen-Ying, Casanova, Jean-Laurent, Kuijpers, Taco, Burns, Jane, Levin, Michael, Hayday, Adrian, and Sancho-Shimizu, Vanessa

Subjects
Humans, COVID-19, Child, Systemic Inflammatory Response Syndrome, Male, Female, Butyrophilins, SARS-CoV-2, Child, Preschool, Heterozygote, Adolescent, Genetic Predisposition to Disease, Infant
Abstract

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, burdenMC, which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.2, 95% CI: 3.5-5.3, P < 10-6). BTNL8 encodes an intestinal epithelial regulator of Vγ4+γδ T cells implicated in regulating gut homeostasis. Enrichment was exclusive to MIS-C, being absent in patients with COVID-19 or bacterial disease. Using an available functional test for BTNL8, rare variants from a larger cohort of MIS-C patients (n = 835) were tested which identified eight variants in 18 patients (2.2%) with impaired engagement of Vγ4+γδ T cells. Most of these variants were in the B30.2 domain of BTNL8 implicated in sensing epithelial cell status. These findings were associated with altered intestinal permeability, suggesting a possible link between disrupted gut homeostasis and MIS-C-associated enteropathy triggered by SARS-CoV-2.

Published
2024

6. Multiple Myeloma Risk and Outcomes Are Associated with Pathogenic Germline Variants in DNA Repair Genes.

Author

Thibaud, Santiago, Subaran, Ryan, Newman, Scott, Lagana, Alessandro, Melnekoff, David, Bodnar, Saoirse, Ram, Meghana, Soens, Zachry, Genthe, William, Brander, Tehilla, Mouhieddine, Tarek, Van Oekelen, Oliver, Houldsworth, Jane, Cho, Hearn, Richard, Shambavi, Richter, Joshua, Rodriguez, Cesar, Rossi, Adriana, Sanchez, Larysa, Chari, Ajai, Moshier, Erin, Jagannath, Sundar, Parekh, Samir, and Onel, Kenan

Subjects
Humans, Multiple Myeloma, Germ-Line Mutation, Female, DNA Repair, Male, Genetic Predisposition to Disease, Middle Aged, Aged, Adult
Abstract

First-degree relatives of patients with multiple myeloma are at increased risk for the disease, but the contribution of pathogenic germline variants (PGV) in hereditary cancer genes to multiple myeloma risk and outcomes is not well characterized. To address this, we analyzed germline exomes in two independent cohorts of 895 and 786 patients with multiple myeloma. PGVs were identified in 8.6% of the Discovery cohort and 11.5% of the Replication cohort, with a notable presence of high- or moderate-penetrance PGVs (associated with autosomal dominant cancer predisposition) in DNA repair genes (3.6% and 4.1%, respectively). PGVs in BRCA1 (OR = 3.9, FDR < 0.01) and BRCA2 (OR = 7.0, FDR < 0.001) were significantly enriched in patients with multiple myeloma when compared with 134,187 healthy controls. Five of the eight BRCA2 PGV carriers exhibited tumor-specific copy number loss in BRCA2, suggesting somatic loss of heterozygosity. PGVs associated with autosomal dominant cancer predisposition were associated with younger age at diagnosis, personal or familial cancer history, and longer progression-free survival after upfront high-dose melphalan and autologous stem-cell transplantation (P < 0.01). Significance: Our findings suggest up to 10% of patients with multiple myeloma may have an unsuspected cancer predisposition syndrome. Given familial implications and favorable outcomes with high-dose melphalan and autologous stem-cell transplantation in high-penetrance PGV carriers, genetic testing should be considered for young or newly diagnosed patients with a personal or family cancer history. See related commentary by Walker, p. 375.

Published
2024

9. Identifying gaps in the conservation of small wild cats of Southeast Asia

Author

Chiaverini, Luca, Macdonald, David W., Hearn, Andrew J., Kaszta, Żaneta, Ash, Eric, Can, Özgün Emre, Channa, Phan, Cheyne, Susan M., Clements, Gopalasamy Reuben, Haidir, Iding Achmad, Kamler, Jan F., Kyaw, Pyae Phyoe, Luskin, Matthew S., Rasphone, Akchousanh, Singh, Priya, Tan, Cedric Kai Wei, Yadav, Bhupendra P., and Cushman, Samuel A.

Published
2025
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12. Comprehensive molecular profiling of multiple myeloma identifies refined copy number and expression subtypes.

Author

Skerget, Sheri, Penaherrera, Daniel, Chari, Ajai, Jagannath, Sundar, Siegel, David, Vij, Ravi, Orloff, Gregory, Jakubowiak, Andrzej, Niesvizky, Ruben, Liles, Darla, Berdeja, Jesus, Levy, Moshe, Wolf, Jeffrey, Usmani, Saad, Christofferson, Austin, Nasser, Sara, Aldrich, Jessica, Legendre, Christophe, Benard, Brooks, Miller, Chase, Turner, Bryce, Kurdoglu, Ahmet, Washington, Megan, Yellapantula, Venkata, Adkins, Jonathan, Cuyugan, Lori, Boateng, Martin, Helland, Adrienne, Kyman, Shari, McDonald, Jackie, Reiman, Rebecca, Stephenson, Kristi, Tassone, Erica, Blanski, Alex, Livermore, Brianne, Kirchhoff, Meghan, Rohrer, Daniel, DAgostino, Mattia, Gamella, Manuela, Collison, Kimberly, Stumph, Jennifer, Kidd, Pam, Donnelly, Andrea, Zaugg, Barbara, Toone, Maureen, McBride, Kyle, DeRome, Mary, Rogers, Jennifer, Craig, David, Liang, Winnie, Gutierrez, Norma, Jewell, Scott, Carpten, John, Anderson, Kenneth, Cho, Hearn, Auclair, Daniel, Lonial, Sagar, and Keats, Jonathan

Subjects
Humans, Multiple Myeloma, DNA Copy Number Variations, Gene Expression Regulation, Neoplastic, Exome Sequencing, Gene Expression Profiling, Female, Male, Whole Genome Sequencing, Longitudinal Studies, Disease Progression, Middle Aged
Abstract

Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundations Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study ( NCT01454297 ) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n = 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are the target of recurrent gain-of-function and loss-of-function events. Consensus clustering identified 8 and 12 unique copy number and expression subtypes of myeloma, respectively, identifying high-risk genetic subtypes and elucidating many of the molecular underpinnings of these unique biological groups. Analysis of serial samples showed that 25.5% of patients transition to a high-risk expression subtype at progression. We observed robust expression of immunotherapy targets in this subtype, suggesting a potential therapeutic option.

Published
2024

13. Validation of Biomechanical Computed Tomography for Fracture Risk Classification in Metastatic Hormone-sensitive Prostate Cancer.

Author

Lin, John, Hearn, Caleb, Getzen, Emily, Long, Qi, Lee, David, Keaveny, Tony, Jayadevappa, Ravishankar, Robinson, Kyle, Wong, Yu-Ning, Maxwell, Kara, Narayan, Vivek, Haas, Naomi, Takvorian, Samuel, Bikle, Daniel, Chiang, Janet, Khan, Amna, Rajapakse, Chamith, Morgans, Alicia, and Parikh, Ravi

Subjects
Androgen deprivation therapy, Antiresorptive therapy, Biomechanical computed tomography, Dual x-ray absorptiometry, Fracture, Prostate cancer, Humans, Male, Prostatic Neoplasms, Aged, Retrospective Studies, Bone Density, Tomography, X-Ray Computed, Risk Assessment, Fractures, Bone, Middle Aged, Androgen Antagonists, Absorptiometry, Photon, Cohort Studies, Biomechanical Phenomena
Abstract

BACKGROUND: Guidelines recommend dual-energy x-ray absorptiometry (DXA) screening to assess fracture risk and benefit from antiresorptive therapy in men with metastatic hormone-sensitive prostate cancer (mHSPC) on androgen deprivation therapy (ADT). However,

Published
2024

15. Institutional Effects of Adding Football: A Difference-in-Difference Analysis

Author

Welch Suggs, Alex B. Monday, Jennifer May-Trifiletti, and James C. Hearn

Abstract

Football teams draw the largest crowds of any American collegiate sport, and with them, both positive and negative attention for colleges and universities. Nearly 50 colleges have added the sport recently, but little research has examined the institutional effects of adding a team. Some of these institutions are regional research universities adding the sport as part of broad plans to transform campus identities, while at smaller public and private institutions, adding a football team (with approximately 100 members) appears to be an attempt to boost racial diversity and the number of male students. This study uses difference-in-difference models to find that adding a football team appears to have a significant, but short-term, effect on enrollment and tuition revenue. The long-term effects of adding the sport do not appear to be statistically significant. This raises questions about the costs and benefits of adding football at a time when higher education faces significant challenges attracting students.

Published
2024
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16. Climate-driven global redistribution of an ocean giant predicts increased threat from shipping

Author

Womersley, Freya C., Sousa, Lara L., Humphries, Nicolas E., Abrantes, Kátya, Araujo, Gonzalo, Bach, Steffen S., Barnett, Adam, Berumen, Michael L., Lion, Sandra Bessudo, Braun, Camrin D., Clingham, Elizabeth, Cochran, Jesse E. M., de la Parra, Rafael, Diamant, Stella, Dove, Alistair D. M., Duarte, Carlos M., Dudgeon, Christine L., Erdmann, Mark V., Espinoza, Eduardo, Ferreira, Luciana C., Fitzpatrick, Richard, Cano, Jaime González, Green, Jonathan R., Guzman, Hector M., Hardenstine, Royale, Hasan, Abdi, Hazin, Fábio H. V., Hearn, Alex R., Hueter, Robert E., Jaidah, Mohammed Y., Labaja, Jessica, Ladino, Felipe, Macena, Bruno C. L., Meekan, Mark G., Morris, Jr., John J., Norman, Bradley M., Peñaherrera-Palma, Cesar R., Pierce, Simon J., Quintero, Lina Maria, Ramírez-Macías, Dení, Reynolds, Samantha D., Robinson, David P., Rohner, Christoph A., Rowat, David R. L., Sequeira, Ana M. M., Sheaves, Marcus, Shivji, Mahmood S., Sianipar, Abraham B., Skomal, Gregory B., Soler, German, Syakurachman, Ismail, Thorrold, Simon R., Thums, Michele, Tyminski, John P., Webb, D. Harry, Wetherbee, Bradley M., Queiroz, Nuno, and Sims, David W.

Published
2024
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18. Phase 1 study combining elotuzumab with autologous stem cell transplant and lenalidomide for multiple myeloma.

Author

Coffey, David, Osman, Keren, Aleman, Adolfo, Bekri, Selma, Kats, Simone, Dhadwal, Amishi, Catamero, Donna, Kim-Schulze, Seunghee, Gnjatic, Sacha, Chari, Ajai, Parekh, Samir, Jagannath, Sundar, and Cho, Hearn

Subjects
hematologic neoplasms, immunotherapy, transplantation immunology, tumor microenvironment, Humans, Lenalidomide, Multiple Myeloma, Hematopoietic Stem Cell Transplantation, Leukocytes, Mononuclear, Transplantation, Autologous, Stem Cell Transplantation, Tumor Microenvironment, Antibodies, Monoclonal, Humanized
Abstract

BACKGROUND: Autologous stem cell transplantation (ASCT) after induction therapy improves disease-free survival for patients with multiple myeloma (MM). While the goal of ASCT is to render a minimal disease state, it is also associated with eradication of immunosuppressive cells, and we hypothesize that early introduction of immunotherapy post-ASCT may provide a window of opportunity to boost treatment efficacy. METHODS: We conducted a phase 1 clinical trial to investigate the application of autologous lymphocyte infusion and anti-SLAMF7 monoclonal antibody, elotuzumab, after ASCT in patients with newly diagnosed MM previously treated with induction therapy. In addition to CD34+ stem cells, peripheral blood mononuclear cells were harvested prior to transplant and infused on day 3 after stem cell infusion to accelerate immune reconstitution and provide autologous natural killer (NK) cells that are essential to the mechanism of elotuzumab. Elotuzumab was administered starting on day 4 and then every 28 days after until 1 year post-ASCT. Cycles 4-12 were administered with standard-of-care lenalidomide maintenance. RESULTS: All subjects were evaluated for safety, and 13 of 15 subjects completed the treatment protocol. At 1 year post-ASCT, the disease status of enrolled subjects was as follows: five stringent complete responses, one complete response, six very good partial responses, one partial response, and two progressive diseases. The treatment plan was well tolerated, with most grade 3 and 4 AEs being expected hematologic toxicities associated with ASCT. Correlative analysis of the immune microenvironment demonstrated a trend toward reduced regulatory T cells during the first 3 months post-transplant followed by an increase in NK cells and monocytes in patients achieving a complete remission. CONCLUSIONS: This phase 1 clinical trial demonstrates that early introduction of immunotherapy after ASCT is well tolerated and shows promising disease control in patients with MM, accompanied by favorable changes in the immune microenvironment. TRIAL REGISTRATION NUMBER: NCT02655458.

Published
2024

19. Streptococcus pyogenes emm Type 3.93 Emergence, the Netherlands and England

Author

Matthew A. Davies, Brechje de Gier, Rebecca L. Guy, Juliana Coelho, Alje P. van Dam, Robin van Houdt, Sébastien Matamoros, Marit van den Berg, Patrick E. Habermehl, Kartyk Moganeradj, Yan Ryan, Steve Platt, Henry Hearn, Eleanor Blakey, Darren Chooneea, Bart J.M. Vlaminckx, Theresa Lamagni, and Nina M. van Sorge

Subjects
Streptococcus pyogenes, streptococci, pneumonia, meningitis/encephalitis, bacteria, epidemiology, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

A global increase in the incidence of invasive group A Streptococcus (iGAS) infections was observed after lifting of COVID-19 related restrictions in 2022, and type M1UK dominated in many countries. After seasonal declines in iGAS incidence during the summer of 2023, simultaneous, rapid expansion of a previously rare emm type 3.93 was seen beginning in November, increasing to 20% of all cases in England and 60% of all cases in the Netherlands within 4 months. emm3.93 was associated with iGAS in children 6–17 years of age and with increased risk for pneumonia or pleural empyema and meningitis in both countries. No excess risk of death was identified for emm3.93 compared with other types. Genomic analysis of historic and contemporary emm3.93 isolates revealed the emergence of 3 new clades with a potentially advantageous genomic configuration. Our findings demonstrate the value of molecular surveillance, including long-read sequencing, in identifying clinical and public health threats.

Published
2025
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23. Prevalence and impact of diabetes on survival of patients with multiple myeloma in different racial groups.

Author

Shah, Urvi, Moshier, Erin, Derkach, Andriy, Huang, Yuanhui, Mailankody, Sham, Tan, Carlyn, Maclachlan, Kylee, Hultcrantz, Malin, Korde, Neha, Hassoun, Hani, Thibaud, Santiago, Sanchez, Larysa, Rodriguez, Cesar, Richard, Shambavi, Richter, Joshua, Rossi, Adriana, Cho, Hearn, Lesokhin, Alexander, Usmani, Saad, Jagannath, Sundar, Parekh, Samir, Gallagher, Emily, and Chari, Ajai

Subjects
Animals, Humans, Mice, Diabetes Mellitus, Homeodomain Proteins, Multiple Myeloma, Prevalence, Racial Groups, Retrospective Studies, White People, Black People, Survival Rate
Abstract

Multiple myeloma (MM) is twice as common in Black individuals compared with in White individuals, and diabetes mellitus (DM) disproportionately affects Black patients. Although numerous studies have shown a correlation between DM and MM, this has not been studied in the context of race and in vivo mechanisms. We conducted a retrospective clinical study of 5383 patients with MM of which 15% had DM (White, 12% and Black, 25%). Multivariable Cox models showed reduced overall survival (OS) for patients with DM (hazard ratio, 1.27; 95% confidence interval, 1.11-1.47; P < .001). This appeared to be driven by a marked difference in OS between White patients with and without DM but not in Black patients. In contrast, obesity was associated with better OS in Black patients but not in White patients. To complement this analysis, we assessed MM growth in a genetically engineered immunocompromised nonobese diabetic (Rag1-/-/muscle creatinine kinase promoter expression of a human IGF1R [M] with a lysine [K] to arginine [R] point mutation) mouse model to evaluate the mechanisms linking DM and MM. MM.1S xenografts grew in more Rag1-/-/MKR mice and grew more rapidly in the Rag1-/-/MKR mice compared with in controls. Western blot analysis found that MM1.S xenografts from Rag1-/-/MKR mice had higher phosphorylated S6 ribosomal protein (Ser235/236) levels, indicating greater activation of the mammalian target of rapamycin pathway. Our study is, to our knowledge, the first to evaluate racial differences in DM prevalence and survival in MM, as well as the effect of DM on tumor growth in mouse models. Our results suggest that DM may contribute to the higher incidence of MM in Black patients; and to improve survival in MM, DM management cannot be ignored.

Published
2024

24. Identifying remnant biodiversity hotspots in Southern Asia reveals disequilibrium in mammalian communities

Author

Sartor, Caroline Charão, Kaszta, Zaneta, Kamler, Jan, Hearn, Andrew J., Ash, Eric, Bolongon, Gilmoore, Can, Özgün Emre, Channa, Phan, Cheyne, Susan, Fitzmaurice, Amy, Haidir, Iding Achmad, Kyaw, Pyae Phyoe, Luskin, Matthew Scott, Singh, Priya, Rasphone, Akchousanh, Wei, Cedric Tan Kai, Yadav, Bhupendra Prasad, Cushman, Samuel A., and Macdonald, David W.

Published
2024
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25. Genome-wide association studies unveil major genetic loci driving insecticide resistance in Anopheles funestus in four eco-geographical settings across Cameroon

Author

Mahamat Gadji, Jonas A. Kengne-Ouafo, Magellan Tchouakui, Murielle J. Wondji, Leon M. J. Mugenzi, Jack Hearn, Onana Boyomo, and Charles S. Wondji

Subjects
Genomic, Anopheles funestus, Cameroon, PoolSeq, Selective sweeps, P450s, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background Insecticide resistance is jeopardising malaria control efforts in Africa. Deciphering the evolutionary dynamics of mosquito populations country-wide is essential for designing effective and sustainable national and subnational tailored strategies to accelerate malaria elimination efforts. Here, we employed genome-wide association studies through pooled template sequencing to compare four eco-geographically different populations of the major vector, Anopheles funestus, across a South North transect in Cameroon, aiming to identify genomic signatures of adaptive responses to insecticides. Results Our analysis revealed limited population structure within Northern and Central regions (F ST 0.049). Greater genetic differentiation was observed at known resistance-associated loci, resistance-to-pyrethroids 1 (rp1) (2R chromosome) and CYP9 (X chromosome), with varying signatures of positive selection across populations. Allelic variation between variants underscores the pervasive impact of selection pressures, with rp1 variants more prevalent in Central and Northern populations (F ST >0.3), and the CYP9 associated variants more pronounced in the Littoral/Coastal region (F ST =0.29). Evidence of selective sweeps was supported by negative Tajima’s D and reduced genetic diversity in all populations, particularly in Central (Elende) and Northern (Tibati) regions. Genomic variant analysis identified novel missense mutations and signatures of complex genomic alterations such as duplications, deletions, transposable element (TE) insertions, and chromosomal inversions, all associated with selective sweeps. A 4.3 kb TE insertion was fixed in all populations with Njombe Littoral/Coastal population, showing higher frequency of CYP9K1 (G454A), a known resistance allele and TE upstream compared to elsewhere. Conclusion Our study uncovered regional variations in insecticide resistance candidate variants, emphasizing the need for a streamlined DNA-based diagnostic assay for genomic surveillance across Africa. These findings will contribute to the development of tailored resistance management strategies crucial for addressing the dynamic challenges of malaria control in Cameroon.

Published
2024
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26. Hybrid Service Delivery for voluntary, community and social enterprise organisations working with adults with learning disabilities and/or autism: a realist review protocol

Author

Danielle Varley, Kris Southby, Joanne Trigwell, Sally SJ Brown, Nicola Lines, Amy Hearn, and Anne-Marie Bagnall

Subjects
Hybrid service delivery, Learning disabilities, Autism, Voluntary and community sector, Digital, Realist review, Medicine
Abstract

Abstract Background Delivery of health and care services using a combination of remote and/or in-person channels and digital and/or traditional tools (Hybrid Service Delivery, HSD) is increasingly seen as a way of improving quality and affordability, improving access, personalisation and sustainability, and reducing inequalities. Across the voluntary, community and social enterprise sector (VCSE), using a combination of remote and/or in-person channels and digital and/or traditional tools (HSD) has enabled the essential provision of services for people who have learning disabilities and/or autistic (LDA). However, it is unclear how different tools and channels have been used, what worked well or not well, for whom, and in what circumstances. The aim of this realist review is to explore how VCSE organisations can effectively use digital technologies alongside or instead of in-person activity to provide social care services to adults with learning disabilities and/or autism. This review protocol is presented in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P). Methods We will conduct a participatory realist review. Following realist review methodology, and involving people with LDA and organisations who deliver services to them, we will define the scope of the review/theory development, search for and appraise evidence, extract and synthesise findings, and develop the narrative. Using a developed strategy, electronic databases (Academic Search Complete, CINAHL, MEDLINE, PsycInfo, SCOPUS, Social Science Citation Index and Social Policy and Practice) will be searched. A data extraction table will be used to assist in sifting, sorting and organising relevant information from identified studies. For each proposition statement, relevant data from the identified literature will be synthesised and compared with the proposed theory to develop an understanding of how, why and when hybrid delivery works in different settings with different populations. Discussion This review aims to collate and synthesise evidence relating to hybrid service delivery in VCSE organisations to provide social care services to LDA adults. By conducting a participatory realist review, we anticipate that the findings will lead to a greater understanding of contextual factors and therefore more relevant recommendations. Systematic review registration PROSPERO CRD42024457161.

Published
2024
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27. Temporal evolution of insecticide resistance and bionomics in Anopheles funestus, a key malaria vector in Uganda

Author

Ambrose Oruni, Magellan Tchouakui, Carlos S. Djoko Tagne, Jack Hearn, Jonathan Kayondo, and Charles S. Wondji

Subjects
Insecticide resistance, Anopheles funestus, Genetic markers, Temporal, Phenotypes, Uganda, Medicine, Science
Abstract

Abstract Insecticide resistance escalation is decreasing the efficacy of vector control tools. Monitoring vector resistance is paramount in order to understand its evolution and devise effective counter-solutions. In this study, we monitored insecticide resistance patterns, vector population bionomics and genetic variants associated with resistance over 3 years from 2021 to 2023 in Uganda. Anopheles funestus s.s was the predominant species in Mayuge but with evidence of hybridization with other species of the An. funestus group. Sporozoite infection rates were relatively very high with a peak of 20.41% in March 2022. Intense pyrethroid resistance was seen against pyrethroids up to 10-times the diagnostic concentration but partial recovery of susceptibility in PBO synergistic assays. Among bednets, only PBO-based nets (PermaNet 3.0 Top and Olyset Plus) and chlorfenapyr-based net (Interceptor G2) had high mortality rates. Mosquitoes were fully susceptible to chlorfenapyr and organophosphates, moderately resistant to clothianidin and resistant to carbamates. The allele frequency of key P450, CYP9K1, resistance marker was constantly very high but that for CYP6P9A/b were very low. Interestingly, we report the first detection of resistance alleles for Ace1 gene (RS = ~ 13%) and Rdl gene (RS = ~ 21%, RR = ~ 4%) in Uganda. The qRT-PCR revealed that Cytochrome P450s CYP9K1, CYP6P9A, CYP6P9b, CYP6P5 and CYP6M7 were consistently upregulated while a glutathione-S-transferase gene (GSTE2) showed low expression. Our study shows the complexity of insecticide resistance patterns and underlying mechanisms, hence constant and consistent spatial and temporal monitoring is crucial to rapidly detect changing resistance profiles which is key in informing deployment of counter interventions.

Published
2024
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28. Case Study: Culturally Responsive School Leadership Employed during a Massive School-Merger/Consolidation in a Large Southeastern Michigan Urban School District during Austere Times

Author

James A. Hearn

Abstract

In 2009, a major metropolitan urban school district in Southeastern Michigan, under state emergency management, implemented a massive school restructuring plan affecting 100+ elementary, middle, and high schools. The consequences of the plan included a high turnover rate of staff and students, violence at local school campuses, low morale among teachers and principals, and forced early retirement for many. The consolidation/merger process presented challenges for principals of merging schools who needed to adopt new leadership behaviors to manage their new school communities. This study aimed to identify Culturally Responsive School Leadership behaviors employed by three urban school principals and its impact on curricular decisions, students, parents, and community engagement levels. These principals created positive schooling experiences, increasing African American and Hispanic students, parents, and community engagement amidst challenges and while leading under state emergency management. The research focused on three principals' implementation of Culturally Responsive School Leadership behaviors that contributed to positive educational experiences and increased engagement levels. The research revealed that: 1) participants showed various critical self-reflections on leadership and decision-making; 2) participants recognized the significance of integrating students' indigenous social-cultural capital and community epistemologies; 3) participants were aware of the socio-economic status of their students and community, understood they could not continue with the limited historical role of schools, had to change the narrative by involving their school, creating overlapping spaces between the school and the community while using school spaces for students, parents, and community needs; 4) participants were aware of the historical marginalization and understood their communities' lived experiences by employing their activism and advocacy to help their students and communities with social justice issues they were experiencing; 5) participants' leadership background, personal experiences, and identities impacted their leadership behaviors; and 6) participants exhibited courageous leadership during uncertain times, fierce charter school competition, accountability, job insecurity, and neoliberal policies. The results of this study suggest Culturally Responsive School Leadership, specifically tailored and in harmony with the needs of African American students, parents, and communities, creates positive educational experiences and increased engagement. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

Published
2024

29. 'It's All about Context': Building School Capacity to Implement a Whole-School Approach to Bullying

Author

Natasha Pearce, Helen Monks, Narelle Alderman, Lydia Hearn, Sharyn Burns, Kevin Runions, Jacinta Francis, and Donna Cross

Abstract

Student bullying behaviours are a significant social issue in schools worldwide. Whilst school staff have access to quality bullying prevention interventions, schools can face significant challenges implementing the whole-school approach required to address the complexity of these behaviours. This study aimed to understand how schools' capacity to implement whole-school bullying prevention interventions could be strengthened to promote sustainability and improve student outcomes. Qualitative methods were used to observe schools over time to gain insight into their implementation capacity to improve student social and emotional wellbeing and prevent and ameliorate harm from bullying. A four-year longitudinal, multi-site case study intensively followed eight schools' implementation of "Friendly Schools," an Australian evidenced-based whole-school bullying prevention intervention. Regular in-depth interviews with school leaders and implementation teams over four years led to the refinement of a staged-implementation process and capacity building tools and revealed four common drivers of implementation quality: (1) strong, committed leadership; (2) organisational structures, processes and resources; (3) staff competencies and commitment; and (4) translating evidence into local school policy and practice. This paper considers the strengths of qualitative data in understanding how and why bullying prevention interventions work as well as actions schools can take to enhance their implementation and sustainability of complex social interventions.

Published
2024
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30. Correction: Can flash glucose monitoring improve glucose management for Aboriginal and Torres Strait Islander peoples with type 2 diabetes? A protocol for a randomised controlled trial

Author

Hachem, Mariam, Hearn, Tracey, Kelly, Ray, Eer, Audrey, Moore, Belinda, Sommerville, Christine, Atkinson-Briggs, Sharon, Twigg, Stephen, Freund, Meagan, O’Neal, David, Story, David, Brown, Alex, McLean, Anna, Sinha, Ashim, Furler, John, O’Brien, Richard, Tran-Duy, An, Clarke, Philip, Braat, Sabine, Koye, Digsu N., Eades, Sandra, Burchill, Luke, and Ekinci, Elif

Published
2024
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31. Can flash glucose monitoring improve glucose management for Aboriginal and Torres Strait Islander peoples with type 2 diabetes? A protocol for a randomised controlled trial

Author

Hachem, Mariam, Hearn, Tracey, Kelly, Ray, Eer, Audrey, Moore, Belinda, Sommerville, Christine, Atkinson-Briggs, Sharon, Twigg, Stephen, Freund, Meagan, O’Neal, David, Story, David, Brown, Alex, McLean, Anna, Sinha, Ashim, Furler, John, O’Brien, Richard, Tran-Duy, An, Clarke, Philip, Braat, Sabine, Koye, Digsu N., Eades, Sandra, Burchill, Luke, and Ekinci, Elif

Published
2024
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35. IVIg Use Associated with Ten-Fold Reduction of Serious Infections in Multiple Myeloma Patients Treated with Anti-BCMA Bispecific Antibodies.

Author

Lancman, Guido, Parsa, Kian, Kotlarz, Krzysztof, Avery, Lisa, Lurie, Alaina, Lieberman-Cribbin, Alex, Cho, Hearn, Parekh, Samir, Richard, Shambavi, Richter, Joshua, Rodriguez, Cesar, Rossi, Adriana, Sanchez, Larysa, Thibaud, Santiago, Jagannath, Sundar, and Chari, Ajai

Subjects
Humans, Multiple Myeloma, Immunoglobulins, Intravenous, Antibodies, Bispecific, B-Cell Maturation Antigen, Agammaglobulinemia, Retrospective Studies
Abstract

UNLABELLED: BCMA-targeted bispecific antibodies (BiAb) are efficacious in relapsed/refractory multiple myeloma; however, serious infections have emerged as important toxicities. In this retrospective study, we characterized all infections and their risk factors, and evaluated the impact of infection prophylaxis in patients treated with BCMA-targeted BiAbs. Among 37 patients, 15 (41%) experienced a grade 3-5 infection, with two infection-related deaths during deep remissions. Most (84%) infections occurred during disease remissions. The cumulative probability of grade 3-5 infection increased over time with no plateau. Among responders (n = 26), profound hypogammaglobulinemia occurred in 100% and continued throughout the entire duration of treatment. During periods when patients were receiving intravenous immunoglobulin (IVIg), the rate of grade 3-5 infections was 90% lower than during observation (incidence rate ratio, 0.10; 95% confidence interval, 0.01-0.80; P = 0.0307). No other risk factors for infection were identified. This study demonstrates that profound hypogammaglobulinemia is universal with BCMA-targeted BiAbs, with intravenous immunoglobulin potentially abrogating most of the infection risk. SIGNIFICANCE: To the best of our knowledge, this is the first study to comprehensively analyze risk factors and mitigation strategies to prevent infections in myeloma patients receiving anti-BCMA bispecific antibodies. Profound and prolonged hypogammaglobulinemia was universal among responders, while immunoglobulin replacement was associated with 90% lower rates of grade 3-5 infections. See related commentary by Garfall and Stadtmauer, p. 427 . This article is featured in Selected Articles from This Issue, p. 419.

Published
2023

36. ZipIt! Merging Models from Different Tasks without Training

Author

Stoica, George, Bolya, Daniel, Bjorner, Jakob, Ramesh, Pratik, Hearn, Taylor, and Hoffman, Judy

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning
Abstract

Typical deep visual recognition models are capable of performing the one task they were trained on. In this paper, we tackle the extremely difficult problem of combining distinct models with different initializations, each solving a separate task, into one multi-task model without any additional training. Prior work in model merging permutes one model to the space of the other then averages them together. While this works for models trained on the same task, we find that this fails to account for the differences in models trained on disjoint tasks. Thus, we introduce "ZipIt!", a general method for merging two arbitrary models of the same architecture that incorporates two simple strategies. First, in order to account for features that aren't shared between models, we expand the model merging problem to allow for merging features within each model by defining a general "zip" operation. Second, we add support for partially zipping the models up until a specified layer, naturally creating a multi-head model. We find that these two changes combined account for 20-60% improvement over prior work, making it more feasible to merge models trained on disjoint tasks without retraining.

Published
2023

37. Higher dose corticosteroids in hospitalised COVID-19 patients requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trialResearch in context

Author

O. Abani, A. Abbas, F. Abbas, J. Abbas, K. Abbas, M. Abbas, S. Abbasi, H. Abbass, A. Abbott, N. Abdallah, A. Abdelaziz, M. Abdelfattah, B. Abdelqader, A. Abdul, B. Abdul, S. Abdul, A. Abdul Rasheed, A. Abdulakeem, R. Abdul-Kadir, A. Abdullah, A. Abdulmumeen, R. Abdul-Raheem, N. Abdulshukkoor, K. Abdusamad, Y. Abed El Khaleq, M. Abedalla, A. Abeer Ul Amna, L. Abel, K. Abernethy, M. Abeywickrema, C. Abhinaya, A. Abidin, A. Aboaba, A. Aboagye-Odei, C. Aboah, H. Aboelela, H. Abo-Leyah, K. Abouelela, A. Abou-Haggar, M. Abouibrahim, A. Abousamra, M. Abouzaid, M. Abraham, T. Abraham, A. Abraheem, J. Abrams, R. Abrams, H.J. Abu, A. Abu-Arafeh, S.M. Abubacker, A. Abung, Y. Abusamra, Y. Aceampong, A. Achara, D. Acharya, F. Acheampong, P. Acheampong, S. Acheampong, J. Acheson, S. Achieng, A. Acosta, R. Acquah, C. Acton, J. Adabie-Ankrah, P. Adair, A.S. Adam, F. Adam, M. Adam, H. Adamali, M. Adamczyk, C. Adams, D. Adams, K. Adams, L. Adams, N. Adams, R. Adams, T. Adams, L. Adamu-Ikeme, K. Adatia, K. Adcock, L. Addai-Boampong, A. Addo, O. Adeagbo, A. Adebiyi, O. Adedeji, Y. Adegeye, K. Adegoke, V. Adell, S. Adenwalla, F.W. Adeoye, O.A. Adesemoye, E.O. Adewunmi, A. Adeyanju, J. Adeyemi, T. Adeyemo, B. Adhikari, S.A. Adhikari, R. Adhikary, A. Aditya, P. Adjepong, G. Adkins, A. Adnan, M. Adriaanse, J. Aeron-Thomas, D. Affleck, C. Afnan, M. Afridi, P. Afrim, F.A. Afriyie, Z.A. Aftab, A. Afum-Adjei Awuah, M. Agarwal, P.N. Agasiya, R. Agbeko, C. Agbo, S. Aggarwal, A. Aghababaie, L. Aguilar Jimenez, J.A. Agyekum, K. Agyen, E.K. Ahadome, S. Ahamed Sadiq, M.H. Ahammed Nazeer, M. Ahmad, S. Ahmad, A. Ahmed, B.A.R. Ahmed, B. Ahmed, F. Ahmed, H. Ahmed, I. Ahmed, K. Ahmed, L. Ahmed, M. Ahmed, M.C. Ahmed, M.S. Ahmed, N. Ahmed, O. Ahmed, R.A. Ahmed, R. Ahmed, S. Ahmed, S.G. Ahmed, S.H. Ahmed, R. Ahmed Ali, B. Ahmed Mohamud, S. Ahmer, A. Ahonia, C. Aidoo, C. Aiken, D. Ail, M. Ainsworth, M. Aissa, L. Aitken, B. Ajay, A. Ajibode, A. Ajmi, N. Akhtar, S. Akili, B. Akinbiyi, O. Akindolie, Y. Akinfenwa, O. Akinkugbe, I. Akinpelu, M. Akram, O. Aktinade, U. Akudi, A.S.A.R. Al Aaraj, A. Al Balushi, M. Al Dakhola, A. Al Swaifi, E. Al-Abadi, A. Alabi, N. Aladangady, M. Alafifi, A. Alam, S. Alam, A. Al-Asadi, K. Alatzoglou, P. Albert, A. Albertus, L. Albon, A. Alcala, G. Alcorn, S. Alcorn, A. Aldana, D. Alderdice, A. Aldesouki, R. Aldouri, J. Aldridge, N. Aldridge, R. Ale, R.M. Ale, A. Alegria, A. Alexander, C. Alexander, J. Alexander, P.D.G. Alexander, J. Al-fori, L. Alghazawi, O. Alhabsha, B. Al-Hakim, R. Alhameed, M. Al-Hayali, S. Al-Hity, A. Ali, F.R. Ali, J. Ali, M. Ali, M.S. Ali, N. Ali, O. Ali, R. Ali, S. Ali, E. Aliberti, J. Alin, A. Alina, A. Alipustain, B. Alisjahbana, F. Aliyuda, K. Alizadeh, M. Al-Jibury, S. Al-Juboori, M. Al-Khalil, A. Alkhudhayri, M. Alkhusheh, F. Allan, N. Allan, A. Allanson, R. Allcock, E. Allen, J. Allen, K. Allen, L. Allen, P. Allen, R. Allen, S. Allen, T. Allen, A. Alli, K. Allison, B. Allman, H.K. Allsop, L. Allsop, D. Allsup, A.F.T. Almahroos, H. Al-Moasseb, M. Al-Obaidi, L. Alomari, A. Al-Rabahi, B. Al-Ramadhani, Z. Al-Saadi, R. Al-Sammarraie, I. Alshaer, R. Al-Shahi Salman, W. Al-Shamkhani, F. Alsheikh, B. Al-Sheklly, S. Altaf, A. Alty, M. Alvarez, M. Alvarez Corral, E. Alveyn, M. Alzetani, S. Amamou, N. Amar, S. Ambalavanan, R. Ambrogetti, C. Ambrose, A. Ameen, A. Amelia Ganefianty, K. Ames, M.R. Amezaga, A. Amin, K. Amin, S. Amin, T. Amin, B. Amit, A. Amjad, N. Amjad, J. Amoah-Dankwa, A. Amoako-Adusei, V. Amosun, M. Amsal, K. Amsha, J. Amuasi, N. Amutio Martin, P. Amy, A. Anada, A. Anand, S. Anandappa, S.D. Anantapatnaikuni, N.K.N. Andari, E. Anderson, J. Anderson, L. Anderson, M. Anderson, N. Anderson, R. Anderson, S. Anderson, W. Anderson, P. Andreou, A. Andrews, J. Andrews, K. Aneke, A. Ang, W.W. Ang, T. Angel, A. Angela, P. Angelini, L. Anguvaa, O. Anichtchik, M. Anim-Somuah, K. Aniruddhan, J. Annett, L. Anning, M. Ansah, P.J. Anstey, R. Anstey, A. Anthony, A. Anthony-Pillai, P. Antill, Z. Antonina, V. Anu, M. Anwar, S. Anwar, E. Apetri, A. Apostolopoulos, S. Appleby, D. Appleyard, M.F. Aquino, B. Araba, S. Aransiola, M. Araujo, A. Archer, D. Archer, S. Archer, D. Arcoria, C. Ardley, G. Arhin-Sam, A.-M. Arias, O. Aribike, R. Arimoto, N.L.P.E. Arisanti, C. Arkley, C. Armah, I. Armata, J. Armistead, A. Armitage, C. Armstrong, M. Armstrong, S. Armstrong, W. Armstrong, P. Armtrong, H. Arndt, C. Arnison-Newgass, D. Arnold, R. Arnold, A. Arnott, D. Arora, K. Arora, P. Arora, R. Arora, A. Arter, A. Arthur, N.M. Artini, A. Arumaithurai, A. Arya, R. Arya, D. Aryal, D. Asandei, G.A. Asare, A. Asghar, M. Asghar, A. Ashab, C. Ashbrook-Raby, H. Ashby, J. Ashcroft, S. Ashcroft, G. Asher, Z. Ashfak, A. Ashfaq, H.A. Asiamah, A. Ashish, D. Ashley, S. Ashman-Flavell, S. Ashok, A.-E.-A. Ashour, M.Z. Ashraf, S. Ashraf, M.B. Ashraq, D. Ashton, S. Ashton, A. Ashworth, F.J. Ashworth, R. Ashworth, A. Aslam, I. Aslam, S. Aslam, L. Aslett, H. Asogan, A. Asrar, O. Assaf, R. Astin-Chamberlain, Y.E. Atabudzi, P. Athavale, D. Athorne, B. Atkins, C. Atkins, S. Atkins, J. Atkinson, V. Atkinson, A. Atomode, B. Atraskiewicz, A.A. Attia, E. Attubato, M. Attwood, P. Aubrey, Z. Auer, A. Aujayeb, A.T. Aung, H. Aung, H.W.W. Aung, K.K. Aung, K.T. Aung, N. Aung, Y. Aung, Z.M. Aung, E. Austin, K. Austin, A. Auwal, M. Avari, M. Avery, N. Aveyard, J. Avis, G. Aviss, C. Avram, P. Avram, A. Awadelkareem, G. Awadzi, M. Awaly, A. Awan, S. Awisi, A. Aya, E. Ayaz, J.M. Ayerh, A. Ayers, J. Azam, A. Azeem, M. Azharuddin, A. Aziz, G. Aziz, I. Aziz, N. Aziz, A. Azkoul, A. Azman Shah, G. Azzopardi, H. Azzoug, F. Babatunde, M. Babi, B. Babiker, G. Babington, M. Babirecki, M. Babores, A.O. Babs-Osibodu, T. Bac, S. Bacciarelli, R. Bachar, M.-E. Bachour, A. Bachti, G. Bacon, J. Bacon, B. Badal, A. Badat, M. Bader, G.R. Badhan, S. Badhrinarayanan, J.P. Bae, A. Baggaley, A. Baggott, G. Bagley, D. Bagmane, L. Bagshaw, K. Bahadori, Y. Bahurupi, A. Bailey, J. Bailey, K. Bailey, L. Bailey, M.A. Bailey, M. Bailey, P. Bailey, S. Bailey, H. Baillie, J.K. Baillie, J. Bain, V. Bains, D. Baird, E. Baird, K. Baird, S. Baird, T. Baird, Y. Baird, A. Bajandouh, M. Bajracharya, D.C. Baker, E. Baker, J. Baker, K. Baker, M. Baker, R. Baker, T.-A. Baker, V. Baker, H. Bakere, N. Bakerly, M. Baker-Moffatt, A. Bakhai, N. Bakhtiar, P. Bakoulas, D. Bakthavatsalam, N. Balachandran, A. Balan, P. Balasingam, T. Balaskas, M. Balasubramaniam, N. Balatoni, A. Balcombe, A. Baldwin, C. Baldwin, D. Baldwin, F. Baldwin, R. Baldwin-Jones, N. Bale, J. Balfour, M. Ball, Ro Ball, K. Ballard, I. Balluz, C. Balmforth, E. Balogh, A. Baltmr, A. Baluwala, G. Bambridge, A. Bamford, P. Bamford, A. Bamgboye, E. Bancroft, H. Bancroft, J. Banda, K. Bandaru, S. Bandi, N. Bandla, S. Bandyopadhyam, A. Banerjee, R. Banerjee, P. Bang, S. Baniya, O. Bani-Saad, H. Banks, L. Banks, P. Banks, C. Bann, H. Bannister, O. Bannister, L. Banton, D.G. Bao, T. Bao, M. Baptist, T. Baqai, A.M. Baral, S.C. Baral, D. Baramova, R. Barber, E. Barbon, M. Barbosa, J. Barbour, A. Barclay, C. Barclay, G. Bardsley, S. Bareford, S. Bari, M. Barimbing, A. Barker, D. Barker, E. Barker, H. Barker, J. Barker, L. Barker, O. Barker, K. Barker-Williams, S. Barkha, J. Barla, G. Barlow, R. Barlow, V. Barlow, J. Barnacle, A. Barnard, D. Barnes, N. Barnes, R. Barnes, T. Barnes, C. Barnetson, A. Barnett, A. Barnett-Vanes, P.G. Barning, W. Barnsley, A. Barr, D. Barr, J. Barr, C. Barr, N. Barratt, S. Barratt, M. Barrera, A. Barrett, Fi Barrett, J. Barrett, S. Barrett, E. Barrow, J. Bartholomew, M.S. Barthwal, C. Bartlett, G. Bartlett, J. Bartlett, L. Bartlett, S. Bartley, S. Bartolmeu-Pires, A. Barton, G. Barton, J. Barton, L. Barton, R. Barton, R. Baruah, S. Baryschpolec, H. Bashir, A. Bashyal, B. Basker, S. Basnet, B. Basnyat, A. Basoglu, A. Basran, J. Bassett, G. Bassett, C. Bassford, B. Bassoy, V. Bastion, A. Bastola, A. Basumatary, P. Basvi, J.A. Batac, V.R. Bataduwaarachchi, T. Bate, H.J. Bateman, K. Bateman, V. Bateman, E. Bates, H. Bates, M. Bates, S. Bates, S. Batham, A. Batista, A. Batla, D. Batra, H. Batty, T. Batty, A. Batty, M. Baum, R. Baumber, C. Bautista, F. Bawa, T. Bawa, F.S. Bawani, S. Bax, M. Baxter, N. Baxter, Z. Baxter, H. Bayes, L.-A. Bayo, F. Bazari, R. Bazaz, A. Bazli, L. Beacham, W. Beadles, K. Beadon, P. Beak, A. Beale, K. Beard, J. Bearpark, A. Beasley, S. Beattie, K. Beaumont, D. Beaumont-Jewell, T. Beaver, S. Beavis, C. Beazley, S. Beck, V. Beckett, R. Beckitt, S. Beckley, H. Beddall, S. Beddows, D. Beeby, S. Beeby, G. Beech, M. Beecroft, N. Beer, Sa Beer, J. Beety, G. Bega, A. Begg, S. Begg, S. Beghini, A. Begum, S. Begum, T. Behan, R. Behrouzi, J. Beishon, C. Beith, J. Belcher, H. Belfield, K. Belfield, A. Belgaumkar, D. Bell, G. Bell, J. Bell, L. Bell, N. Bell, P. Bell, S. Bell, J. Bellamu, M. Bellamy, T. Bellamy, A. Bellini, A. Bellis, F. Bellis, L. Bendall, N. Benesh, N. Benetti, S.A. Bengu, L. Benham, G. Benison-Horner, S. Benkenstein, T. Benn, A. Bennett, C. Bennett, D. Bennett, G. 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Blackledge, J. Blackler, S. Blackley, H. Blackman, C. Blackstock, C. Blair, F. Blakemore, H. Blamey, A. Bland, S. Blane, S. Blankley, P. Blaxill, K. Blaylock, J. Blazeby, N. Blencowe, B. Bloom, J. Bloomfield, A. Bloss, A. Blowers, S. Blows, H. Bloxham, S. Blrd, L. Blundell, A. Blunsum, M. Blunt, T. Blunt, I. Blyth, K. Blyth, A. Blythe, K. Blythe, K.A. Boahen, M. Boampoaa, S. Board, E. Boatemah, B. Bobie, K. Bobruk, P.N. Bodalia, N. Bodasing, M. Boden, T. Bodenham, G. Boehmer, M. Boffito, K. Bohanan, K. Bohmova, N. Bohnacker, S. Bokhandi, M. Bokhar, S. Bokhari, S.O. Bokhari, I. Bokobza, A. Boles, C. Bolger, C. Bonaconsa, C. Bond, H. Bond, S. Bond, T. Bond, A. Bone, G. Boniface, J. Bonney, L. Bonney, L. Booker, S. Boot, M. Boothroyd, J. Borbone, N. Borman, S. Bosence, K. Bostock, N. Botting, F. Bottrill, H. Bouattia, L. Bough, H. Boughton, Z. Boult, T. Boumrah, M. Bourke, S. Bourke, M. Bourne, R. Bousfield, L. Boustred, A. Bowes, P. Bowker, T. Bowker, H. Bowler, L. Bowman, S. Bowman, R. 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Williamson, J. Williamson, J.D. Williamson, R. Williamson, H. Williamson, E. Willis, H. Willis, J. Willis, L. Wills, L. Willsher, C. Willshire, F. Willson, J. Willson, A. Wilson, B. Wilson, D. Wilson, I. Wilson, J. Wilson, K. Wilson, K.-A. Wilson, L. Wilson, M. Wilson, S. Wilson, T. Wilson, K.L.Y. Win, M. Win, T. Win, T.T. Win, W.Y.W. Win, L. Winckworth, L. Winder, P. Winder, S. Winearl, H. Winmill, S. Winn, C. Winpenny, H. Winslow, H. Winter, J. Winter, B. Winter-Goodwin, J. Winterton, H. Winwood, J. Wischhusen, S. Wisdom, M. Wise, M. Wiselka, R. Wiseman, S. Wiseman, S. Wishart, T. WIshlade, E. Witele, N. Withers, J. Wittes, D. Wixted, T. Wodehouse, W. Wolf, N. Wolff, K. Wolffsohn, R. Wolf-Roberts, E. Wolodimeroff, A. Wolstencroft, A. Wong, C. Wong, C.-H. Wong, C.-M. Wong, E. Wong, J.S.Y. Wong, K.Y. Wong, M.Y. Wong, N. Wong, S. Wong, T. Wong, A.A. Wongkyezeng, A. Wood, C. Wood, D. Wood, F. Wood, G. Wood, H. Wood, J. Wood, L. Wood, M. Wood, S. Wood, T. Wood, K. Woodall, R. Woodfield, C. Woodford, E. Woodford, J. Woodford, L. Woodhead, T. Woodhead, P. Woodland, M. Woodman, S. Woodmansey, C. Woods, J. Woods, K. Woods, S. Woods, Z. Woodward, M. Woolcock, G. Wooldridge, R. Woolf, C. Woollard, L. Woollen, E. Woolley, J. Woolley, D. Woosey, D. Wootton, J. Wootton, D. Worley, S. Worton, J. Wraight, M. Wray, K. Wren, L. Wren, C. Wrey Brown, C. Wright, D. Wright, F. Wright, H. Wright, I. Wright, L. Wright, R. Wright, S. Wright, T. Wright, C. Wroe, H. Wroe, H. Wu, P. Wu, J. Wubetu, F. Wulandari, R. Wulandari, S. Wurie, C. Wyatt, F. Wyn-Griffiths, I. Wynter, B. Xavier, A. Xhikola, B.E. Xia, Z. Xia, E. Yacoba, S. Yadav, M. Yakubi, M. Yan, Y. Yanagisawa, F. Yang, Y. Yang, M. Yanney, W.L. Yap, N. Yaqoob, S. Yasmin, B. Yates, D. Yates, E. Yates, H. Yates, T. Yates, M. Yates, J. Ye, C. Yearwood Martin, K. Yein, F. Yelnoorkar, L. Yen, L.M. Yen, A. Yeoh, C.Y. Yeung, P. Yew, D. Yewatkar, L. Ylquimiche Melly, I. Ynter, H. Yong, J. Yorke, J. Youens, A. Younes Ibrahim, E. Young, G. Young, L. Young, A. Yousafzar, S. Youssouf, A. Yousuf, H. Yovita, C. Yu, J.S.J. Yuan, N. Yufaniaputri, B. Yung, D. Yusef, S. Yusef, I. Yusuf, A.-S. Zafar, S. Zagalo, S. Zaher, A. Zahoor, M. Zainab, T. Zak, K. Zaki, N. Zakir, K. Zalewska, A. Zamalloa, M. Zaman, S. Zaman, J. Zamikula, L. Zammit, M. Zammit-Mangion, M. Zawadzka, M. Zayed, E. Zebracki, D. Zehnder, L. Zeidan, D. Zeinali, J. Zhang, X. Zhao, D. Zheng, D. Zhu, M. Zia, O. Zibdeh, R. Zill-E-Huma, E.T. Zin, E. Zincone, G. Zindoga, E. Zinkin, V. Zinyemba, C. Zipitis, L. Zitter, A. Zmierczak, G. Zubikarai, A. Zubir, N. Zuhra, R. Zulaikha, S. Zulfikar, C. Zullo, and A. Zuriaga-Alvaro

Subjects
COVID-19, Corticosteroid, Dexamethasone, Mortality, Clinical trial, Medicine (General), R5-920
Abstract

Summary: Background: Low dose corticosteroids (e.g., 6 mg dexamethasone) have been shown to reduce mortality for hypoxic COVID-19 patients. We have previously reported that higher dose corticosteroids cause harm in patients with clinical hypoxia but not receiving ventilatory support (the combination of non-invasive mechanical ventilation, including high-flow nasal oxygen, continuous positive airway pressure and bilevel positive airway pressure ventilation, and invasive mechanical ventilation or extra-corporeal membrane oxygenation), but the balance of efficacy and safety in patients receiving ventilatory support is uncertain. Methods: This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) assessed multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients receiving ventilatory support were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg once daily for 5 days or until discharge if sooner) or usual standard of care alone (which includes dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. Recruitment closed on 31 March 2024 when funding for the trial ended. The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). Findings: Between 25 May 2021 and 9 January 2024, 477 COVID-19 patients receiving ventilatory support were randomly allocated to receive usual care plus higher dose corticosteroids vs. usual care alone (of whom 99% received corticosteroids during the follow-up period). Of those randomised, 221 (46%) were in Asia, 245 (51%) in the UK and 11 (2%) in Africa. 143 (30%) had diabetes mellitus. Overall, 86 (35%) of 246 patients allocated to higher dose corticosteroids vs. 86 (37%) of 231 patients allocated to usual care died within 28 days (rate ratio [RR] 0.87; 95% CI 0.64–1.18; p = 0.37). There was no significant difference in the proportion of patients discharged from hospital alive within 28 days (128 [52%] in the higher dose corticosteroids group vs. 120 [52%] in the usual care group; RR 1.04, 0.81–1.33]; p = 0.78). Among those not on invasive mechanical ventilation at baseline, there was no clear reduction in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (76 [37%] of 206 vs. 93 [45%] of 205; RR 0.79 [95% CI 0.63–1.00]; p = 0.05). Interpretation: In patients hospitalised for COVID-19 receiving ventilatory support, we found no evidence that higher dose corticosteroids reduced the risk of death compared to usual care, which included low dose corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute for Health Research (Grant ref: MC_PC_19056), and Wellcome Trust (Grant Ref: 222406/Z/20/Z).

Published
2025
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38. Evolution of texture and residual stresses in 2205 duplex stainless steel during laser powder bed fusion

Author

Steve Gaudez, Florencia Malamud, William Hearn, Shieren Sumarli, Markus Strobl, and Steven Van Petegem

Subjects
Additive manufacturing, Residual strains/stresses, Bragg-edge imaging, Neutron diffraction, In situ/operando, Materials of engineering and construction. Mechanics of materials, TA401-492
Abstract

This study investigates the development of residual stresses in textured 2205 duplex stainless steel during laser powder bed fusion additive manufacturing (LPBF AM). In situ and operando neutron diffraction experiments were conducted to study the transient and real-time evolution of stresses and strains during processing, using an AM machine designed for neutron studies. Additionally, Bragg-edge imaging was employed to investigate the crystallographic texture. The results showed that residual stress redistribution primarily occurs in the first set of added layers when further layers are added on top. The cube texture observed in the sample significantly affects residual stress determination, leading to inaccuracies up to 96 MPa if not accounted for. This highlights the need for orientation-dependent diffraction elastic constants in residual stress calculations. Furthermore, variations in texture intensity across the sample dimensions were found to be driven by changes in the local temperature history, which were deciphered from real-time strain measurements. Finally, this study demonstrates the potential of combining LPBF with neutron diffraction to investigate the underlying mechanisms of AM in the bulk of the sample.

Published
2025
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39. Feasibility and effectiveness of a group therapy combining physical activity, surf therapy and cognitive behavioral therapy to treat adolescents with depressive disorders: a pilot study

Author

Bettina Hearn, Monica Biscaldi, Reinhold Rauh, and Christian Fleischhaker

Subjects
adolescence, depression, group therapy, physical activity, surf therapy, feasibility, Psychology, BF1-990
Abstract

IntroductionThe high prevalence of depression among adolescents underlines the need for further research into effective treatment options. Previous research has demonstrated the effectiveness of physical activity in reducing depressive symptoms. Recently, studies on surf therapy, as an innovative approach of physical activity, have shown promising results regarding the reduction of depressive symptoms in adults and the improvement of general mental health problems in adolescents. However, research in this area is still limited. The aim of the current study was to investigate the feasibility and effectiveness of a group therapy program that combines physical activity, including surf therapy, with cognitive behavioral therapy for treating depression among adolescents.MethodsThirty-two outpatients (28 female, four male) aged 13–18 years with a mean age of 15.58 years (SD = 1.52) and a primary diagnosis of depression were included. They participated in a 3-month group therapy program in groups of eight adolescents. The dropout rate was calculated as an aspect of feasibility. To evaluate effectiveness, depressive symptoms were assessed using the “Children's Depression Rating Scale–Revised” (CDRS-R) as the primary outcome measure at pre-program, post-program, and at 3-month follow-up. In addition, questionnaires assessing depressive symptoms [“Beck Depression Inventory II” (BDI-II)], emotion regulation strategies [“Fragebogen zur Erhebung der Emotionsregulation bei Kindern und Jugendlichen” (FEEL-KJ)] and self-esteem [“Selbstwertinventar für Kinder und Jugendliche” [SEKJ)] were administered as secondary outcome measures.ResultsResults showed a low dropout rate of 9.38% (n = 3). Depressive symptoms, assessed by the CDRS-R, were significantly reduced over time, with a large effect size. Symptom reductions were maintained at the 3-month follow-up.DiscussionStudy results suggest that the group therapy program is feasible and can reduce depressive symptoms. Further research that includes control groups is needed. As a clinical implication, novel treatment forms which integrate elements of physical activity, should be considered as a treatment option for depressed adolescents

Published
2025
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40. Sensemaking with AI: How trust influences Human-AI collaboration in health and creative industries

Author

Sarah J. Daly, Greg Hearn, and Kyriaki Papageorgiou

Subjects
Trust, Artificial intelligence, Sensemaking, Human-AI collaboration, Persona methodology, History of scholarship and learning. The humanities, AZ20-999, Social sciences (General), H1-99
Abstract

This study investigates how trust influences human-AI collaboration within the health and creative sectors, where attitudes toward AI vary widely due to field-specific challenges and expectations. By comparing perspectives from 285 professionals, including artists and doctors, and through persona narratives, we explore how trust in AI can enhance human potential and encourage adoption. Findings reveal that trust hinges on transparency, contextual understanding, human agency during collaboration, and the user's initial perception of AI. This study contributes to understanding trust as a cornerstone of successful human-AI collaboration, proposing ways to foster trusted AI adoption across diverse professional landscapes.

Published
2025
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