78 results on '"Delaney S"'
Search Results
2. Spatial and Temporal Limits of the Casas Grandes Tradition: A View from the Fronteras Valley
- Author
-
John Philip Carpenter, Guadalupe Sánchez, Edson Cupa, Alejandra Abrego-Rivas, José Antonio López-Rivera, Claudia Elena León-Romero, Andrew R. Krug, Jaron T. Davidson, Dakota Larrick, Justin R. Lund, Delaney S. Cooley, and Matthew C. Pailes
- Subjects
Archeology ,History - Abstract
This article revises the spatial and temporal boundaries of the Casas Grandes tradition associated with northwest Chihuahua, Mexico, based on new data collected in neighboring northeastern Sonora. The Casas Grandes tradition attained its greatest extent during the Medio period (AD 1200–1450/1500) followed by a dramatic demographic and political collapse. Hunter-gatherer groups subsequently occupied most of northwest Chihuahua. Data from the Fronteras Valley, Sonora, presents an alternative scenario, with a clear pattern of cultural continuity from the eleventh century to the colonial period in which sedentary farmers occupied the same landscapes and occasionally the same villages. These observations contribute to our understanding of the spread and subsequent demise of the Casas Grandes tradition in hinterland regions. For the Fronteras Valley, we infer that immigrant groups originally introduced Casas Grandes traditions and that uneven participation in a suite of shared religious beliefs and practices was common to all the hinterlands.
- Published
- 2022
3. The expendables: Bioarchaeological evidence for pauper apprentices in 19th century England and the health consequences of child labour
- Author
-
Gowland, Rebecca L., primary, Caffell, Anwen C., additional, Quade, Leslie, additional, Levene, Alysa, additional, Millard, Andrew R., additional, Holst, Malin, additional, Yapp, Poppy, additional, Delaney, S., additional, Brown, Chloe, additional, Nowell, Geoff, additional, McPherson, Colin, additional, Shaw, Heidi A., additional, Stewart, Nicolas A., additional, Robinson, Sally, additional, Montgomery, Janet, additional, and Alexander, Michelle M., additional
- Published
- 2023
- Full Text
- View/download PDF
4. Displacement imposition scale assesses reactions of cigarette and e-cigarette users impacted by a campus-wide smoking ban
- Author
-
Thad R. Leffingwell, Ashley B. Cole, Emma I. Brett, Susanna V. Lopez, Emily A Warner, Delaney S. Dunn, and Eleanor L S Leavens
- Subjects
Demographics ,Scale (social sciences) ,Environmental health ,Single factor ,Tobacco control ,Public Health, Environmental and Occupational Health ,Computer-assisted web interviewing ,Smoking ban ,Psychology ,Displacement (psychology) ,Article ,Denormalization - Abstract
Objective The present study developed a measure assessing the emotional responses, "Displacement Imposition," of cigarette and e-cigarette users on a college campus with a smoking/vaping ban. It also examined the relationship between Displacement Imposition and readiness to quit smoking/vaping, and how this relationship differed between cigarette and e-cigarette users. Participants Participants (N = 297) were from a large, Midwestern university. Methods Participants completed online questionnaires assessing demographics, cigarette and e-cigarette use, Displacement Imposition, and readiness to quit. Results All six Displacement Imposition items loaded onto a single factor. A significant interaction emerged between Displacement Imposition and product use in predicting readiness to quit. At high levels of Displacement Imposition, cigarette users were less ready to quit than e-cigarette users. Conclusions Findings suggest restrictions imposed on cigarette and e-cigarette users were associated with reduced readiness to quit. Findings inform tobacco control policies as tobacco denormalization may increase the burden placed on tobacco users.
- Published
- 2021
5. The expendables: Bioarchaeological evidence for pauper apprentices in 19th century England and the health consequences of child labour.
- Author
-
Gowland, Rebecca L., Caffell, Anwen C., Quade, Leslie, Levene, Alysa, Millard, Andrew R., Holst, Malin, Yapp, Poppy, Delaney, S., Brown, Chloe, Nowell, Geoff, McPherson, Colin, Shaw, Heidi A., Stewart, Nicolas A., Robinson, Sally, Montgomery, Janet, and Alexander, Michelle M.
- Subjects
CHILD labor ,POOR children ,CHILDREN'S health ,LOW-protein diet ,STABLE isotopes ,OCCUPATIONAL hazards - Abstract
Child labour is the most common form of child abuse in the world today, with almost half of child workers employed in hazardous industries. The large-scale employment of children during the rapid industrialisation of the late 18
th and early 19th centuries in England is well documented. During this period, the removal of pauper children from workhouses in cities to work as apprentices in rural mills in the North of England was commonplace. Whilst the experiences of some of these children have been recorded historically, this study provides the first direct evidence of their lives through bioarchaeological analysis. The excavation of a rural churchyard cemetery in the village of Fewston, North Yorkshire, yielded the skeletal remains of 154 individuals, including an unusually large proportion of children aged between 8 to 20 years. A multi-method approach was undertaken, including osteological and palaeopathological examination, stable isotope and amelogenin peptide analysis. The bioarchaeological results were integrated with historical data regarding a local textile mill in operation during the 18th -19th centuries. The results for the children were compared to those obtained from contemporaneous individuals of known identity (from coffin plates) of comparable date. Most of the children exhibited distinctive 'non-local' isotope signatures and a diet low in animal protein when compared to the named local individuals. These children also showed severe growth delays and pathological lesions indicative of early life adversity, as well as respiratory disease, which is a known occupational hazard of mill work. This study has provided unique insights into the harrowing lives of these children; born into poverty and forced to work long hours in dangerous conditions. This analysis provides a stark testimony of the impacts of industrial labour on the health, growth and mortality risk of children, with implications for the present as well as our understanding of the past. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
6. A system mapping activity to visualize lithium’s interconnectedness to societal and environmental aspects of the green energy transition
- Author
-
Delaney Seamus, Donnelly Scott, Rochette Emily, and Orgill MaryKay
- Subjects
lithium ,concept mapping ,e-waste ,systems thinking ,schoolteachers ,Chemistry ,QD1-999 - Abstract
Lithium’s role in the global green energy transition provides an engaging context to visualize the interconnectedness of chemistry to seismic shifts taking place in society. Lithium has seen a dramatic increase in utilization, but given lithium’s current low rates of recyclability, this development is exacerbating the e-waste problem. Equally important, we posit that lithium extraction, from either brine or ore, and the associated impacts on the environment and local communities should not be so easily decoupled from the shift in human behaviors causing its demand. Presented here is a mapping activity that was trialed in professional learning workshops organized in New Zealand for secondary/high school chemistry teachers. In their mapping activity response, the teachers were able to connect typical school chemistry content (batteries, chemical processes) with environmental (planetary systems) and social, economic, and ethical considerations (useful products, unintended consequences, inequity in access to water) of the ongoing electrification of society. The teachers indicated a positive intention to utilize the activity, or one similar with a different chemical process or product, in their own classrooms. A school-ready version of the activity is provided in the supplementary information, which was revised based on feedback from the teachers attending the workshops.
- Published
- 2024
- Full Text
- View/download PDF
7. 219 IMPROVING DELIRIUM SCREENING AND MANAGEMENT IN POST-ACUTE REHABILITATION: A MULTI-STAGE QUALITY IMPROVEMENT INITIATIVE
- Author
-
McDaid, E, primary, Harte, A, additional, Reynolds, A, additional, Hearne, S, additional, Synnott, E, additional, Buckley, E, additional, Delaney, S, additional, and Cogan, L, additional
- Published
- 2021
- Full Text
- View/download PDF
8. Results of an international crowdsourcing survey on the treatment of non-ST segment elevation ACS patients at high-bleeding risk undergoing percutaneous intervention
- Author
-
Bhatt, DL, Kaski, JC, Delaney, S, Alasnag, M, Andreotti, F, Angiolillo, DJ, Ferro, A, Gorog, DA, Lorenzatti, AJ, Mamas, M, McNeil, J, Nicolau, JC, Steg, PG, Tamargo, J, Tan, D, and Valgimigli, M
- Abstract
Aims\ud Choosing an antiplatelet strategy in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) at high bleeding risk (HBR), undergoing post-percutaneous coronary intervention (PCI), is complex. We used a unique open-source approach (crowdsourcing) to document if practices varied across a small, global cross-section of antiplatelet prescribers in the post-PCI setting.\ud \ud Methods and results\ud Five-hundred and fifty-nine professionals from 70 countries (the ‘crowd’) completed questionnaires containing single- or multi-option and free form questions regarding antiplatelet clinical practice in post-PCI NSTE-ACS patients at HBR. A threshold of 75% defined ‘agreement’. There was strong agreement favouring monotherapy with either aspirin or a P2Y12 inhibitor following initial DAPT, within the first year (94%). No agreement was reached on the optimal duration of DAPT or choice of monotherapy: responses were in equipoise for shorter (≤3 months, 51%) or longer (≥6 months, 46%) duration, and monotherapy choice (45% aspirin; 53% P2Y12 inhibitor). Most respondents stated use of guideline-directed tools to assess risk, although clinical judgement was preferred by 32% for assessing bleeding risk and by 46% for thrombotic risk.\ud \ud Conclusion\ud The crowdsourcing methodology showed potential as a tool to assess current practice and variation on a global scale and to achieve a broad demographic representation. These preliminary results indicate a high degree of variation with respect to duration of DAPT, monotherapy drug of choice following DAPT and how thrombotic and bleeding risk are assessed. Further investigations should concentrate on interrogating practice variation between key demographic groups.
- Published
- 2021
9. Peritoneal Infusion of Oxygen Microbubbles Alters the Metabolomic Profile of the Lung and Spleen in Acute Hypoxic Exposure
- Author
-
Christina Lisk, Alex Fan, Francesca I. Cendali, Kenta Kakiuchi, Delaney Swindle, David I. Pak, Robert Tolson, Abby Grier, Keely Buesing, Seth Zaeske, Angelo D’Alessandro, Mark A. Borden, and David C. Irwin
- Subjects
Metabolomics ,OMBs ,spleen ,lung ,hypoxia ,Technology ,Biology (General) ,QH301-705.5 - Abstract
Administration of oxygen microbubbles (OMBs) has been shown to increase oxygen and decrease carbon dioxide in systemic circulation, as well as reduce lung inflammation and promote survival in preclinical models of hypoxia caused by lung injury. However, their impact on microenvironmental oxygenation remains unexplored. Herein, we investigated the effects of intraperitoneal administration of OMBs in anesthetized rats exposed to hypoxic ventilation (FiO2 = 0.14). Blood oxygenation and hemodynamics were evaluated over a 2 h time frame, and then organ and tissue samples were collected for hypoxic and metabolic analyses. Data showed that OMBs improved blood SaO2 (~14%) and alleviated tissue hypoxia within the microenvironment of the kidney and intestine at 2 h of hypoxia. Metabolomic analysis revealed OMBs induced metabolic differences in the cecum, liver, kidney, heart, red blood cells and plasma. Within the spleen and lung, principal component analysis showed a metabolic phenotype more comparable to the normoxic group than the hypoxic group. In the spleen, this shift was characterized by reduced levels of fatty acids and 2-hydroxygluterate, alongside increased expression of antioxidant enzymes such as glutathione and hypoxanthine. Interestingly, there was also a shuttle effect within the metabolism of the spleen from the tricarboxylic acid cycle to the glycolysis and pentose phosphate pathways. In the lung, metabolomic analysis revealed upregulation of phosphatidylethanolamine and phosphatidylcholine synthesis, indicating a potential indirect mechanism through which OMB administration may improve lung surfactant secretion and prevent alveolar collapse. In addition, cell-protective purine salvage was increased within the lung. In summary, oxygenation with intraperitoneal OMBs improves systemic blood and local tissue oxygenation, thereby shifting metabolomic profiles of the lung and spleen toward a healthier normoxic state.
- Published
- 2024
- Full Text
- View/download PDF
10. You are not like the rest of them: disrupting meta-perceptions dilutes dehumanization
- Author
-
Kevin R. Carriere, Gregory Hallenbeck, Delaney Sullivan, and Rebecca Ghion
- Subjects
meta-perceptions ,imagined interactions ,text analysis ,meta-perception correction ,dehumanization ,atypicality ,Psychology ,BF1-990 - Abstract
Political polarization, fueled by conflicting meta-perceptions, presents a critical obstacle to constructive discourse and collaboration. These meta-perceptions-how one group perceives another group's views of them-are often inaccurate and can lead to detrimental outcomes such as increased hostility and dehumanization. Across two studies, we introduce and experimentally test a novel approach that exposes participants to atypical, counter-stereotypical members of an opposing group who either confirm or disrupt their existing meta-perceptions. We find that disrupting meta-perceptions decreases dehumanization of the partner, increases interest in wanting to learn more about them, but fails to increase willingness to interact in the future with the partner. We conduct an exploratory text analysis to uncover differences in word choice by condition. Our research adds a new dimension to the existing body of work by examining the efficacy of alternative intervention strategies to improve intergroup relations in politically polarized settings.
- Published
- 2024
- Full Text
- View/download PDF
11. Improving the Generalizability and Performance of an Ultrasound Deep Learning Model Using Limited Multicenter Data for Lung Sliding Artifact Identification
- Author
-
Derek Wu, Delaney Smith, Blake VanBerlo, Amir Roshankar, Hoseok Lee, Brian Li, Faraz Ali, Marwan Rahman, John Basmaji, Jared Tschirhart, Alex Ford, Bennett VanBerlo, Ashritha Durvasula, Claire Vannelli, Chintan Dave, Jason Deglint, Jordan Ho, Rushil Chaudhary, Hans Clausdorff, Ross Prager, Scott Millington, Samveg Shah, Brian Buchanan, and Robert Arntfield
- Subjects
artificial intelligence ,deep learning ,explainability ,generalizability ,lung ultrasound ,lung sliding ,Medicine (General) ,R5-920 - Abstract
Deep learning (DL) models for medical image classification frequently struggle to generalize to data from outside institutions. Additional clinical data are also rarely collected to comprehensively assess and understand model performance amongst subgroups. Following the development of a single-center model to identify the lung sliding artifact on lung ultrasound (LUS), we pursued a validation strategy using external LUS data. As annotated LUS data are relatively scarce—compared to other medical imaging data—we adopted a novel technique to optimize the use of limited external data to improve model generalizability. Externally acquired LUS data from three tertiary care centers, totaling 641 clips from 238 patients, were used to assess the baseline generalizability of our lung sliding model. We then employed our novel Threshold-Aware Accumulative Fine-Tuning (TAAFT) method to fine-tune the baseline model and determine the minimum amount of data required to achieve predefined performance goals. A subgroup analysis was also performed and Grad-CAM++ explanations were examined. The final model was fine-tuned on one-third of the external dataset to achieve 0.917 sensitivity, 0.817 specificity, and 0.920 area under the receiver operator characteristic curve (AUC) on the external validation dataset, exceeding our predefined performance goals. Subgroup analyses identified LUS characteristics that most greatly challenged the model’s performance. Grad-CAM++ saliency maps highlighted clinically relevant regions on M-mode images. We report a multicenter study that exploits limited available external data to improve the generalizability and performance of our lung sliding model while identifying poorly performing subgroups to inform future iterative improvements. This approach may contribute to efficiencies for DL researchers working with smaller quantities of external validation data.
- Published
- 2024
- Full Text
- View/download PDF
12. Diet and Meal Pattern Determinants of Glucose Levels and Variability in Adults with and without Prediabetes or Early-Onset Type 2 Diabetes: A Pilot Study
- Author
-
Leinys S. Santos-Báez, Diana A. Díaz-Rizzolo, Collin J. Popp, Delaney Shaw, Keenan S. Fine, Annemarie Altomare, Marie-Pierre St-Onge, Emily N. C. Manoogian, Satchidananda Panda, Bin Cheng, and Blandine Laferrère
- Subjects
continuous glucose monitoring ,diet composition ,meal timing ,normoglycemic ,dysglycemic ,Nutrition. Foods and food supply ,TX341-641 - Abstract
This observational pilot study examined the association between diet, meal pattern and glucose over a 2-week period under free-living conditions in 26 adults with dysglycemia (D-GLYC) and 14 with normoglycemia (N-GLYC). We hypothesized that a prolonged eating window and late eating occasions (EOs), along with a higher dietary carbohydrate intake, would result in higher glucose levels and glucose variability (GV). General linear models were run with meal timing with time-stamped photographs in real time, and diet composition by dietary recalls, and their variability (SD), as predictors and glucose variables (mean glucose, mean amplitude of glucose excursions [MAGE], largest amplitude of glucose excursions [LAGE] and GV) as dependent variables. After adjusting for calories and nutrients, a later eating midpoint predicted a lower GV (β = −2.3, SE = 1.0, p = 0.03) in D-GLYC, while a later last EO predicted a higher GV (β = 1.5, SE = 0.6, p = 0.04) in N-GLYC. A higher carbohydrate intake predicted a higher MAGE (β = 0.9, SE = 0.4, p = 0.02) and GV (β = 0.4, SE = 0.2, p = 0.04) in N-GLYC, but not D-GLYC. In summary, our data suggest that meal patterns interact with dietary composition and should be evaluated as potential modifiable determinants of glucose in adults with and without dysglycemia. Future research should evaluate causality with controlled diets.
- Published
- 2024
- Full Text
- View/download PDF
13. Extracellular Vesicle Size Reveals Cargo Specific to Coagulation and Inflammation in Pediatric and Adult Sickle Cell Disease
- Author
-
Kiruphagaran Thangaraju PhD, Saini Setua PhD, Christina Lisk PhD, Delaney Swindle MS, Daniel Stephenson PhD, Monika Dzieciatkowska PhD, Derek R. Lamb BS, Parikshit Moitra PhD, David Pak MS, Kathryn Hassell MD, Gemlyn George MD, Rachelle Nuss MD, Pavel Davizon-Castillo MD, Kurt R. Stenmark MD, Angelo D’Alessandro PhD, David C. Irwin PhD, and Paul W. Buehler PharmD, PhD
- Subjects
Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Aberrant coagulation in sickle cell disease (SCD) is linked to extracellular vesicle (EV) exposure. However, there is no consensus on the contributions of small EVs (SEVs) and large EVs (LEVs) toward underlying coagulopathy or on their molecular cargo. The present observational study compared the thrombin potential of SEVs and LEVs isolated from the plasma of stable pediatric and adult SCD patients. Further, EV lipid and protein contents were analyzed to define markers consistent with activation of thrombin and markers of underlying coagulopathy. Results suggested that LEVs—but not SEVs—from pediatrics and adults similarly enhanced phosphatidylserine (PS)-dependent thrombin generation, and cell membrane procoagulant PS (18:0;20:4 and 18:0;18:1) were the most abundant lipids found in LEVs. Further, LEVs showed activated coagulation in protein pathway analyses, while SEVs demonstrated high levels of cholesterol esters and a protein pathway analysis that identified complement factors and inflammation. We suggest that thrombin potential of EVs from both stable pediatric and adult SCD patients is similarly dependent on size and show lipid and protein contents that identify underlying markers of coagulation and inflammation.
- Published
- 2023
- Full Text
- View/download PDF
14. Moderate hypoxia induces metabolic divergence in circulating monocytes and tissue resident macrophages from Berkeley sickle cell anemia mice
- Author
-
Christina Lisk, Francesca Cendali, David I. Pak, Delaney Swindle, Kathryn Hassell, Rachelle Nuss, Gemlyn George, Pavel Davizon-Castillo, Paul W. Buehler, Angelo D’Alessandro, and David C. Irwin
- Subjects
sickle cell disease ,hypoxia ,spleen ,pulmonary hypertension ,metabolic disease ,Medicine (General) ,R5-920 - Abstract
IntroductionHuman and murine sickle cell disease (SCD) associated pulmonary hypertension (PH) is defined by hemolysis, nitric oxide depletion, inflammation, and thrombosis. Further, hemoglobin (Hb), heme, and iron accumulation are consistently observed in pulmonary adventitial macrophages at autopsy and in hypoxia driven rodent models of SCD, which show distribution of ferric and ferrous Hb as well as HO-1 and ferritin heavy chain. The anatomic localization of these macrophages is consistent with areas of significant vascular remodeling. However, their contributions toward progressive disease may include unique, but also common mechanisms, that overlap with idiopathic and other forms of pulmonary hypertension. These processes likely extend to the vasculature of other organs that are consistently impaired in advanced SCD.MethodsTo date, limited information is available on the metabolism of macrophages or monocytes isolated from lung, spleen, and peripheral blood in humans or murine models of SCD.ResultsHere we hypothesize that metabolism of macrophages and monocytes isolated from this triad of tissue differs between Berkley SCD mice exposed for ten weeks to moderate hypobaric hypoxia (simulated 8,000 ft, 15.4% O2) or normoxia (Denver altitude, 5000 ft) with normoxia exposed wild type mice evaluated as controls.DiscussionThis study represents an initial set of data that describes the metabolism in monocytes and macrophages isolated from moderately hypoxic SCD mice peripheral lung, spleen, and blood mononuclear cells.
- Published
- 2023
- Full Text
- View/download PDF
15. P124: A new in-skates balance error scoring system for the sideline assessment of concussion in hockey players
- Author
-
Robert, A., primary, Moroz, M., additional, Var, D., additional, Correa, J., additional, and Delaney, S., additional
- Published
- 2018
- Full Text
- View/download PDF
16. A physiologically relevant 3D collagen-based scaffold–neuroblastoma cell system exhibits chemosensitivity similar to orthotopic xenograft models
- Author
-
Curtin, C., primary, Nolan, J.C., additional, Conlon, R., additional, Deneweth, L., additional, Gallagher, C., additional, Tan, Y.J., additional, Cavanagh, B.L., additional, Asraf, A.Z., additional, Harvey, H., additional, Miller-Delaney, S., additional, Shohet, J., additional, Bray, I., additional, O'Brien, F.J., additional, Stallings, R.L., additional, and Piskareva, O., additional
- Published
- 2018
- Full Text
- View/download PDF
17. Murine models of sickle cell disease and beta‐thalassemia demonstrate pulmonary hypertension with distinctive features
- Author
-
Paul W. Buehler, Delaney Swindle, David I. Pak, Mehdi A. Fini, Kathryn Hassell, Rachelle Nuss, Rebecca B. Wilkerson, Angelo D’Alessandro, and David C. Irwin
- Subjects
lung ,heart ,metabolomics ,pulmonary vascular disease ,hemaglobinopathies ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 ,Diseases of the respiratory system ,RC705-779 - Abstract
Sickle cell anemia and β‐thalassemia intermedia are very different genetically determined hemoglobinopathies predisposing to pulmonary hypertension. The etiologies responsible for the associated development of pulmonary hypertension in both diseases are multi‐factorial with extensive mechanistic contributors described. Both sickle cell anemia and β‐thalassemia intermedia present with intra and extravascular hemolysis. And because sickle cell anemia and β‐thalassemia intermedia share features of extravascular hemolysis, macrophage iron excess and anemia we sought to characterize the common features of the pulmonary hypertension phenotype, cardiac mechanics, and function as well as lung and right ventricular metabolism. Within the concept of iron, we have defined a unique pulmonary vascular iron accumulation in lungs of sickle cell anemia pulmonary hypertension patients at autopsy. This observation is unlike findings in idiopathic or other forms of pulmonary arterial hypertension. In this study, we hypothesized that a common pathophysiology would characterize the pulmonary hypertension phenotype in sickle cell anemia and β‐thalassemia intermedia murine models. However, unlike sickle cell anemia, β‐thalassemia is also a disease of dyserythropoiesis, with increased iron absorption and cellular iron extrusion. This process is mediated by high erythroferrone and low hepcidin levels as well as dysregulated iron transport due transferrin saturation, so there may be differences as well. Herein we describe common and divergent features of pulmonary hypertension in aged Berk‐ss (sickle cell anemia) and Hbbth/3+ (intermediate β‐thalassemia) mice and suggest translational utility as proof‐of‐concept models to study pulmonary hypertension therapeutics specific to genetic anemias.
- Published
- 2021
- Full Text
- View/download PDF
18. Evidence supporting a role for circulating macrophages in the regression of vascular remodeling following sub‐chronic exposure to hemoglobin plus hypoxia
- Author
-
Vijaya Karoor, Delaney Swindle, David I Pak, Julie Harral, Derek Strassheim, Mehdi A Fini, Edward Dempsey, Kurt R Stenmark, Kathryn Hassell, Rachelle Nuss, Paul W. Buehler, and David C. Irwin
- Subjects
lung ,heart ,sickle cell disease ,pulmonary vascular disease ,hemoglobinopathies ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 ,Diseases of the respiratory system ,RC705-779 - Abstract
Macrophages are a heterogeneous population with both pro‐ and anti‐inflammatory functions play an essential role in maintaining tissue homeostasis, promoting inflammation under pathological conditions, and tissue repair after injury. In pulmonary hypertension, the M1 phenotype is more pro‐inflammatory compared to the M2 phenotype, which is involved in tissue repair. The role of macrophages in the initiation and progression of pulmonary hypertension is well studied. However, their role in the regression of established pulmonary hypertension is not well known. Rats chronically exposed to hemoglobin (Hb) plus hypoxia (HX) share similarities to humans with pulmonary hypertension associated with hemolytic disease, including the presence of a unique macrophage phenotype surrounding distal vessels that are associated with vascular remodeling. These lung macrophages are characterized by high iron content, HO‐1, ET‐1, and IL‐6, and are recruited from the circulation. Depletion of macrophages in this model prevents the development of pulmonary hypertension and vascular remodeling. In this study, we specifically investigate the regression of pulmonary hypertension over a four‐week duration after rats were removed from Hb + HX exposure with and without gadolinium chloride administration. Withdrawal of Hb + HX reversed systolic pressures and right ventricular function after Hb + Hx exposure in four weeks. Our data show that depleting circulating monocytes/macrophages during reversal prevents complete recovery of right ventricular systolic pressure and vascular remodeling in this rat model of pulmonary hypertension at four weeks post exposure. The data presented offer a novel insight into the role of macrophages in the processes of pulmonary hypertension regression in a rodent model of Hb + Hx‐driven disease.
- Published
- 2021
- Full Text
- View/download PDF
19. Organised communities build healthier soils
- Author
-
Delaney, S., Garcia, D., White, A., Delaney, S., Garcia, D., and White, A.
- Abstract
Farmers who are trying to build up healthy soil on their land can find it a particularly prolonged process. Work with local community organisation in Nicaragua, however, shows that results can be seen relatively quickly and achieved on a broad scale, with a long-term farmer-led strategy. From its origins in the 1970s, The Council of Protestant Churches in Nicaragua (CEPAD) has been learning continuously and adapting its approach. And one of the key things they have learned is that if farmers want to build healthy soils, they have to start with healthy community organisations.
- Published
- 2015
20. Determining the Effects of Pelleted Cranberry Vine Grains on the Ewe and Offspring during Pregnancy and Lactation
- Author
-
Delaney Smith, Katherine Petersson, and Maria L. Peterson
- Subjects
periparturient ,anthelmintic ,ovine ,milk fat ,condensed tannins ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
When creating any new anti-parasitic interventions, it is important to evaluate their effects across all life stages. This study had three objectives, which were to evaluate the effect of feeding cranberry vine pellet (CVP) on (1) ewes’ body weights and BCS during late gestation and lactation; (2) ewes’ milk quality during lactation; and (3) lambs’ body weight and growth parameters from birth to 65 days of age. Across two years, 41 Dorset ewes were fed either a 50% CVP or a matching control pellet (CON) from 104 ± 1.60 days of gestation for 62.8 ± 0.68 days of lactation. Measurements were collected from ewes (BW, BCS, and milk) and lambs (BW and body size). Milk from CVP ewes exhibited reduced milk fat and solids (p < 0.01) and increased concentrations of milk urea nitrogen (p = 0.02) when evaluated for the treatment–time. There was no significant difference in the BCS, protein, lamb BW, or growth measurements for treatment–time (p ≥ 0.05). Additional research that targets blood biochemistry and metabolic assessments is needed to fully determine the impact of this pellet on ewes and lambs.
- Published
- 2023
- Full Text
- View/download PDF
21. Enhancing Annotation Efficiency with Machine Learning: Automated Partitioning of a Lung Ultrasound Dataset by View
- Author
-
Bennett VanBerlo, Delaney Smith, Jared Tschirhart, Blake VanBerlo, Derek Wu, Alex Ford, Joseph McCauley, Benjamin Wu, Rushil Chaudhary, Chintan Dave, Jordan Ho, Jason Deglint, Brian Li, and Robert Arntfield
- Subjects
computer vision ,machine learning ,annotation ,labelling ,lung ultrasound ,medical imaging ,Medicine (General) ,R5-920 - Abstract
Background: Annotating large medical imaging datasets is an arduous and expensive task, especially when the datasets in question are not organized according to deep learning goals. Here, we propose a method that exploits the hierarchical organization of annotating tasks to optimize efficiency. Methods: We trained a machine learning model to accurately distinguish between one of two classes of lung ultrasound (LUS) views using 2908 clips from a larger dataset. Partitioning the remaining dataset by view would reduce downstream labelling efforts by enabling annotators to focus on annotating pathological features specific to each view. Results: In a sample view-specific annotation task, we found that automatically partitioning a 780-clip dataset by view saved 42 min of manual annotation time and resulted in 55±6 additional relevant labels per hour. Conclusions: Automatic partitioning of a LUS dataset by view significantly increases annotator efficiency, resulting in higher throughput relevant to the annotating task at hand. The strategy described in this work can be applied to other hierarchical annotation schemes.
- Published
- 2022
- Full Text
- View/download PDF
22. Targeting the Maladaptive Effects of Binge Drinking on Circadian Gene Expression
- Author
-
Kolter Grigsby, Courtney Ledford, Tanvi Batish, Snigdha Kanadibhotla, Delaney Smith, Evan Firsick, Alexander Tran, Kayla Townsley, Kaylee-Abril Vasquez Reyes, Katherine LeBlanc, and Angela Ozburn
- Subjects
circadian ,alcohol ,nucleus accumbens ,suprachiasmatic nucleus ,ventral tegmental area ,gene expression ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Previous studies (1) support a role of circadian genes in regulating alcohol intake, and (2) reveal that harmful alcohol use alters circadian rhythms. However, there is minimal knowledge of the effects of chronic alcohol processes on rhythmic circadian gene expression across brain regions important for circadian biology and alcohol intake. Therefore, the present study sought to test the effects of chronic binge-like drinking on diurnal circadian gene expression patterns in the master circadian pacemaker (SCN), the ventral tegmental area (VTA), and the nucleus accumbens (NAc) in High Drinking in the Dark-1 (HDID-1) mice, a unique genetic risk model for drinking to intoxication. Consistent with earlier findings, we found that 8 weeks of binge-like drinking reduced the amplitude of several core circadian clock genes in the NAc and SCN, but not the VTA. To better inform the use of circadian-relevant pharmacotherapies in reducing harmful drinking and ameliorating alcohol’s effects on circadian gene expression, we tested whether the casein kinase-1 inhibitor, PF-67046, or the phosphodiesterase type-4 (an upstream regulator of circadian signalling) inhibitor, apremilast, would reduce binge-like intake and mitigate circadian gene suppression. PF-67046 did not reduce intake but did have circadian gene effects. In contrast, apremilast reduced drinking, but had no effect on circadian expression patterns.
- Published
- 2022
- Full Text
- View/download PDF
23. Yeast Kinesin-5 Motor Protein CIN8 Promotes Accurate Chromosome Segregation
- Author
-
Delaney Sherwin, Abigail Huetteman, and Yanchang Wang
- Subjects
kinesin-5 motor proteins ,Cin8 ,Kip1 ,tension on chromosomes ,tension checkpoint ,Cytology ,QH573-671 - Abstract
Accurate chromosome segregation depends on bipolar chromosome–microtubule attachment and tension generation on chromosomes. Incorrect chromosome attachment results in chromosome missegregation, which contributes to genome instability. The kinetochore is a protein complex that localizes at the centromere region of a chromosome and mediates chromosome–microtubule interaction. Incorrect chromosome attachment leads to checkpoint activation to prevent anaphase onset. Kinetochore detachment activates the spindle assembly checkpoint (SAC), while tensionless kinetochore attachment relies on both the SAC and tension checkpoint. In budding yeast Saccharomyces cerevisiae, kinesin-5 motor proteins Cin8 and Kip1 are needed to separate spindle pole bodies for spindle assembly, and deletion of CIN8 causes lethality in the absence of SAC. To study the function of Cin8 and Kip1 in chromosome segregation, we constructed an auxin-inducible degron (AID) mutant, cin8-AID. With this conditional mutant, we first confirmed that cin8-AID kip1∆ double mutants were lethal when Cin8 is depleted in the presence of auxin. These cells arrested in metaphase with unseparated spindle pole bodies and kinetochores. We further showed that the absence of either the SAC or tension checkpoint was sufficient to abolish the cell-cycle delay in cin8-AID mutants, causing chromosome missegregation and viability loss. The tension checkpoint-dependent phenotype in cells with depleted Cin8 suggests the presence of tensionless chromosome attachment. We speculate that the failed spindle pole body separation in cin8 mutants could increase the chance of tensionless syntelic chromosome attachments, which depends on functional tension checkpoint for survival.
- Published
- 2022
- Full Text
- View/download PDF
24. High-affinity P2Y2 and low-affinity P2X7 receptor interaction modulates ATP-mediated calcium signaling in murine osteoblasts.
- Author
-
Nicholas Mikolajewicz, Delaney Smith, Svetlana V Komarova, and Anmar Khadra
- Subjects
Biology (General) ,QH301-705.5 - Abstract
The P2 purinergic receptor family implicated in many physiological processes, including neurotransmission, mechanical adaptation and inflammation, consists of ATP-gated non-specific cation channels P2XRs and G-protein coupled receptors P2YRs. Different cells, including bone forming osteoblasts, express multiple P2 receptors; however, how P2X and P2Y receptors interact in generating cellular responses to various doses of [ATP] remains poorly understood. Using primary bone marrow and compact bone derived osteoblasts and BMP2-expressing C2C12 osteoblastic cells, we demonstrated conserved features in the P2-mediated Ca2+ responses to ATP, including a transition of Ca2+ response signatures from transient at low [ATP] to oscillatory at moderate [ATP], and back to transient at high [ATP], and a non-monotonic changes in the response magnitudes which exhibited two troughs at 10-4 and 10-2 M [ATP]. We identified P2Y2 and P2X7 receptors as predominantly contributing to these responses and constructed a mathematical model of P2Y2R-induced inositol trisphosphate (IP3) mediated Ca2+ release coupled to a Markov model of P2X7R dynamics to study this system. Model predictions were validated using parental and CRISPR/Cas9-generated P2Y2 and P2Y7 knockouts in osteoblastic C2C12-BMP cells. Activation of P2Y2 by progressively increasing [ATP] induced a transition from transient to oscillatory to transient Ca2+ responses due to the biphasic nature of IP3Rs and the interaction of SERCA pumps with IP3Rs. At high [ATP], activation of P2X7R modulated the response magnitudes through an interplay between the biphasic nature of IP3Rs and the desensitization kinetics of P2X7Rs. Moreover, we found that P2Y2 activity may alter the kinetics of P2X7 towards favouring naïve state activation. Finally, we demonstrated the functional consequences of lacking P2Y2 or P2X7 in osteoblast mechanotransduction. This study thus provides important insights into the biophysical mechanisms underlying ATP-dependent Ca2+ response signatures, which are important in mediating bone mechanoadaptation.
- Published
- 2021
- Full Text
- View/download PDF
25. Yeast Fin1-PP1 dephosphorylates an Ipl1 substrate, Ndc80, to remove Bub1-Bub3 checkpoint proteins from the kinetochore during anaphase.
- Author
-
Michael Bokros, Delaney Sherwin, Marie-Helene Kabbaj, and Yanchang Wang
- Subjects
Genetics ,QH426-470 - Abstract
The spindle assembly checkpoint (SAC) prevents anaphase onset in response to chromosome attachment defects, and SAC silencing is essential for anaphase onset. Following anaphase onset, activated Cdc14 phosphatase dephosphorylates the substrates of cyclin-dependent kinase to facilitate anaphase progression and mitotic exit. In budding yeast, Cdc14 dephosphorylates Fin1, a regulatory subunit of protein phosphatase 1 (PP1), to enable kinetochore localization of Fin1-PP1. We previously showed that kinetochore-localized Fin1-PP1 promotes the removal of the SAC protein Bub1 from the kinetochore during anaphase. We report here that Fin1-PP1 also promotes kinetochore removal of Bub3, the Bub1 partner, but has no effect on another SAC protein Mad1. Moreover, the kinetochore localization of Bub1-Bub3 during anaphase requires Aurora B/Ipl1 kinase activity. We further showed that Fin1-PP1 facilitates the dephosphorylation of kinetochore protein Ndc80, a known Ipl1 substrate. This dephosphorylation reduces kinetochore association of Bub1-Bub3 during anaphase. In addition, we found that untimely Ndc80 dephosphorylation causes viability loss in response to tensionless chromosome attachments. These results suggest that timely localization of Fin1-PP1 to the kinetochore controls the functional window of SAC and is therefore critical for faithful chromosome segregation.
- Published
- 2021
- Full Text
- View/download PDF
26. The Cdc48 Complex Alleviates the Cytotoxicity of Misfolded Proteins by Regulating Ubiquitin Homeostasis
- Author
-
Ryan Higgins, Marie-Helene Kabbaj, Delaney Sherwin, Lauren A. Howell, Alexa Hatcher, Robert J. Tomko, Jr., and Yanchang Wang
- Subjects
proteotoxicity ,Cdc48 ,San1/Ubr1 E3 ligases ,ubiquitin homeostasis ,mutated Huntingtin ,Biology (General) ,QH301-705.5 - Abstract
Summary: The accumulation of misfolded proteins is associated with multiple neurodegenerative disorders, but it remains poorly defined how this accumulation causes cytotoxicity. Here, we demonstrate that the Cdc48/p97 segregase machinery drives the clearance of ubiquitinated model misfolded protein Huntingtin (Htt103QP) and limits its aggregation. Nuclear ubiquitin ligase San1 acts upstream of Cdc48 to ubiquitinate Htt103QP. Unexpectedly, deletion of SAN1 and/or its cytosolic counterpart UBR1 rescues the toxicity associated with Cdc48 deficiency, suggesting that ubiquitin depletion, rather than compromised proteolysis of misfolded proteins, causes the growth defect in cells with Cdc48 deficiency. Indeed, Cdc48 deficiency leads to elevated protein ubiquitination levels and decreased free ubiquitin, which depends on San1/Ubr1. Furthermore, enhancing free ubiquitin levels rescues the toxicity in various Cdc48 pathway mutants and restores normal turnover of a known Cdc48-independent substrate. Our work highlights a previously unappreciated function for Cdc48 in ensuring the regeneration of monoubiquitin that is critical for normal cellular function.
- Published
- 2020
- Full Text
- View/download PDF
27. Regulation of Kv11.1 Isoform Expression by Polyadenylate Binding Protein Nuclear 1
- Author
-
Matthew R. Stump, Rachel T. Nguyen, Rachel H. Drgastin, Delaney Search, Qiuming Gong, and Zhengfeng Zhou
- Subjects
alternative polyadenylation ,hERG ,long QT syndrome ,splicing ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The Kv11.1 voltage-gated potassium channel, encoded by the KCNH2 gene, conducts the rapidly activating delayed rectifier current in the heart. KCNH2 pre-mRNA undergoes alternative polyadenylation to generate two C-terminal Kv11.1 isoforms in the heart. Utilization of a poly(A) signal in exon 15 produces the full-length, functional Kv11.1a isoform, while intron 9 polyadenylation generates the C-terminally truncated, nonfunctional Kv11.1a-USO isoform. The relative expression of Kv11.1a and Kv11.1a-USO isoforms plays an important role in the regulation of Kv11.1 channel function. In this study, we tested the hypothesis that the RNA polyadenylate binding protein nuclear 1 (PABPN1) interacts with a unique 22 nt adenosine stretch adjacent to the intron 9 poly(A) signal and regulates KCNH2 pre-mRNA alternative polyadenylation and the relative expression of Kv11.1a C-terminal isoforms. We showed that PABPN1 inhibited intron 9 poly(A) activity using luciferase reporter assays, tandem poly(A) reporter assays, and RNA pulldown assays. We also showed that PABPN1 increased the relative expression level of the functional Kv11.1a isoform using RNase protection assays, immunoblot analyses, and patch clamp recordings. Our present findings suggest a novel role for the RNA-binding protein PABPN1 in the regulation of functional and nonfunctional Kv11.1 isoform expression.
- Published
- 2021
- Full Text
- View/download PDF
28. ExSeisDat: A set of parallel I/O and workflow libraries for petroleum seismology
- Author
-
Fisher Meghan A., Conbhuí Pádraig Ó., Brion Cathal Ó., Acquaviva Jean-Thomas, Delaney Seán, O’Brien Gareth S., Dagg Steven, Coomer James, and Short Ruairi
- Subjects
Chemical technology ,TP1-1185 ,Energy industries. Energy policy. Fuel trade ,HD9502-9502.5 - Abstract
Seismic data-sets are extremely large and are broken into data files, ranging in size from 100s of GiBs to 10s of TiBs and larger. The parallel I/O for these files is complex due to the amount of data along with varied and multiple access patterns within individual files. Properties of legacy file formats, such as the de-facto standard SEG-Y, also contribute to the decrease in developer productivity while working with these files. SEG-Y files embed their own internal layout which could lead to conflict with traditional, file-system-level layout optimization schemes. Additionally, as seismic files continue to increase in size, memory bottlenecks will be exacerbated, resulting in the need for smart I/O optimization not only to increase the efficiency of read/writes, but to manage memory usage as well. The ExSeisDat (Extreme-Scale Seismic Data) set of libraries addresses these problems through the development and implementation of easy to use, object oriented libraries that are portable and open source with bindings available in multiple languages. The lower level parallel I/O library, ExSeisPIOL (Extreme-Scale Seismic Parallel I/O Library), targets SEG-Y and other proprietary formats, simplifying I/O by internally interfacing MPI-I/O and other I/O interfaces. The I/O is explicitly handled; end users only need to define the memory limits, decomposition of I/O across processes, and data access patterns when reading and writing data. ExSeisPIOL bridges the layout gap between the SEG-Y file structure and file system organization. The higher level parallel seismic workflow library, ExSeisFlow (Extreme-Scale Seismic workFlow), leverages ExSeisPIOL, further simplifying I/O by implicitly handling all I/O parameters, thus allowing geophysicists to focus on domain-specific development. Operations in ExSeisFlow focus on prestack processing and can be performed on single traces, individual gathers, and across entire surveys, including out of core sorting, binning, filtering, and transforming. To optimize memory management, the workflow only reads in data pertinent to the operations being performed instead of an entire file. A smart caching system manages the read data, discarding it when no longer needed in the workflow. As the libraries are optimized to handle spatial and temporal locality, they are a natural fit to burst buffer technologies, particularly DDN’s Infinite Memory Engine (IME) system. With appropriate access semantics or through the direct exploitation of the low-level interfaces, the ExSeisDat stack on IME delivers a significant improvement to I/O performance over standalone parallel file systems like Lustre.
- Published
- 2018
- Full Text
- View/download PDF
29. 3,N4-Etheno-5-methylcytosine blocks TET1-3 oxidation but is repaired by ALKBH2, 3 and FTO.
- Author
-
Ma J, Qi R, Harcourt EM, Chen YT, Barbosa GM, Peng Z, Howarth S, Delaney S, and Li D
- Abstract
5-Methyldeoxycytidine (5mC) is a major epigenetic marker that regulates cellular functions in mammals. Endogenous lipid peroxidation can convert 5mC into 3,N4-etheno-5-methylcytosine (ϵ5mC). ϵ5mC is structurally similar to the mutagenic analog 3,N4-ethenocytosine (ϵC), which is repaired by AlkB family enzymes in the direct reversal repair (DRR) pathway and excised by DNA glycosylases in the base excision repair (BER) pathway. However, the repair of ϵ5mC has not been reported. Here, we examined the activities against ϵ5mC by DRR and BER enzymes and TET1-3, enzymes that modify the 5-methyl group in 5mC. We found that the etheno modification of 5mC blocks oxidation by TET1-3. Conversely, three human homologs in the AlkB family, ALKBH2, 3 and FTO were able to repair ϵ5mC to 5mC, which was subsequently modified by TET1 to 5-hydroxymethylcytosine. We also demonstrated that ALKBH2 likely repairs ϵ5mC in MEF cells. Another homolog, ALKBH5, could not repair ϵ5mC. Also, ϵ5mC is not a substrate for BER glycosylases SMUG1, AAG, or TDG. These findings indicate DRR committed by ALKBH2, 3 and FTO could reduce the detrimental effects of ϵ5mC in genetics and epigenetics and may work together with TET enzymes to modulate epigenetic regulations., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2024
- Full Text
- View/download PDF
30. Limbic Network and Papez Circuit Involvement in ALS: Imaging and Clinical Profiles in GGGGCC Hexanucleotide Carriers in C9orf72 and C9orf72 -Negative Patients.
- Author
-
Christidi F, Kleinerova J, Tan EL, Delaney S, Tacheva A, Hengeveld JC, Doherty MA, McLaughlin RL, Hardiman O, Siah WF, Chang KM, Lope J, and Bede P
- Abstract
Background : While frontotemporal involvement is increasingly recognized in Amyotrophic lateral sclerosis (ALS), the degeneration of limbic networks remains poorly characterized, despite growing evidence of amnestic deficits, impaired emotional processing and deficits in social cognition. Methods : A prospective neuroimaging study was conducted with 204 individuals with ALS and 111 healthy controls. Patients were stratified for hexanucleotide expansion status in C9orf72 . A deep-learning-based segmentation approach was implemented to segment the nucleus accumbens, hypothalamus, fornix, mammillary body, basal forebrain and septal nuclei. The cortical, subcortical and white matter components of the Papez circuit were also systematically evaluated. Results : Hexanucleotide repeat expansion carriers exhibited bilateral amygdala, hypothalamus and nucleus accumbens atrophy, and C9orf72 negative patients showed bilateral basal forebrain volume reductions compared to controls. Both patient groups showed left rostral anterior cingulate atrophy, left entorhinal cortex thinning and cingulum and fornix alterations, irrespective of the genotype. Fornix, cingulum, posterior cingulate, nucleus accumbens, amygdala and hypothalamus degeneration was more marked in C9orf72 -positive ALS patients. Conclusions : Our results highlighted that mesial temporal and parasagittal subcortical degeneration is not unique to C9orf72 carriers. Our radiological findings were consistent with neuropsychological observations and highlighted the importance of comprehensive neuropsychological testing in ALS, irrespective of the underlying genotype.
- Published
- 2024
- Full Text
- View/download PDF
31. Bartonella species bacteremia in association with adult psychosis.
- Author
-
Delaney S, Robveille C, Maggi RG, Lashnits E, Kingston E, Liedig C, Murray L, Fallon BA, and Breitschwerdt EB
- Abstract
Introduction: The potential role of pathogens, particularly vector-transmitted infectious agents, as a cause of psychosis has not been intensively investigated. We have reported a potential link between Bartonella spp. bacteremia and neuropsychiatric symptoms, including pediatric acute onset neuropsychiatric syndrome and schizophrenia. The purpose of this study was to further assess whether Bartonella spp. exposure or infection are associated with psychosis., Methods: In a blinded manner, we assessed the presence of anti- Bartonella antibodies by indirect immunofluorescence assays (IFA), and infection by amplification of bacterial DNA from blood by quantitative polymerase chain reaction (qPCR), digital PCR (dPCR), and droplet digital PCR (ddPCR) in 116 participants. Participants were categorized into one of five groups: 1) controls unaffected by psychosis ( n = 29); 2) prodromal participants ( n = 16); 3) children or adolescents with psychosis ( n = 7); 4) adults with psychosis ( n = 44); and 5) relatives of a participant with psychosis ( n = 20)., Results: There was no significant difference in Bartonella spp. IFA seroreactivity between adults with psychosis and adult controls unaffected by psychosis. There was a higher proportion of adults with psychosis who had Bartonella spp. DNA in the bloodstream (43.2%) compared to adult controls unaffected by psychosis (14.3%, p = 0.021). The Bartonella species was determined for 18 of the 31 bacteremic participants, including infection or co-infection with Bartonella henselae (11/18), Bartonella vinsonii subsp. b erkhoffii (6/18), Bartonella quintana (2/18), Bartonella alsatica (1/18), and Bartonella rochalimae (1/18)., Discussion: In conjunction with other recent research, the results of this study provide justification for a large national or international multi-center study to determine if Bartonella spp. bacteremia is more prevalent in adults with psychosis compared to adults unaffected by psychosis. Expanding the investigation to include a range of vector-borne and other microbial infections with potential CNS effects would enhance knowledge on the relationship between psychosis and infection., Competing Interests: In conjunction with Dr. S. Sontakke and North Carolina State University, EB holds US Patent No. 7,115,385 Media and Methods for Cultivation of Microorganisms, which was issued on October 3rd, 2006. He is a co-founder, shareholder and Chief Scientific Officer for Galaxy Diagnostics, a company that provides advanced diagnostic testing for the detection of Bartonella spp. infections. RM is a co-founder and the Chief Technical Officer for Galaxy Diagnostics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Delaney, Robveille, Maggi, Lashnits, Kingston, Liedig, Murray, Fallon and Breitschwerdt.)
- Published
- 2024
- Full Text
- View/download PDF
32. Association of Environmental Injustice and Cardiovascular Diseases and Risk Factors in the United States.
- Author
-
Khadke S, Kumar A, Al-Kindi S, Rajagopalan S, Kong Y, Nasir K, Ahmad J, Adamkiewicz G, Delaney S, Nohria A, Dani SS, and Ganatra S
- Subjects
- United States epidemiology, Humans, Risk Factors, Cardiovascular Diseases epidemiology, Cardiovascular Diseases prevention & control, Coronary Artery Disease, Hypertension, Stroke epidemiology
- Abstract
Background: While the impacts of social and environmental exposure on cardiovascular risks are often reported individually, the combined effect is poorly understood., Methods and Results: Using the 2022 Environmental Justice Index, socio-environmental justice index and environmental burden module ranks of census tracts were divided into quartiles (quartile 1, the least vulnerable census tracts; quartile 4, the most vulnerable census tracts). Age-adjusted rate ratios (RRs) of coronary artery disease, strokes, and various health measures reported in the Prevention Population-Level Analysis and Community Estimates data were compared between quartiles using multivariable Poisson regression. The quartile 4 Environmental Justice Index was associated with a higher rate of coronary artery disease (RR, 1.684 [95% CI, 1.660-1.708]) and stroke (RR, 2.112 [95% CI, 2.078-2.147]) compared with the quartile 1 Environmental Justice Index. Similarly, coronary artery disease 1.057 [95% CI,1.043-1.0716] and stroke (RR, 1.118 [95% CI, 1.102-1.135]) were significantly higher in the quartile 4 than in the quartile 1 environmental burden module. Similar results were observed for chronic kidney disease, hypertension, diabetes, obesity, high cholesterol, lack of health insurance, sleep <7 hours per night, no leisure time physical activity, and impaired mental and physical health >14 days., Conclusions: The prevalence of CVD and its risk factors is highly associated with increased social and environmental adversities, and environmental exposure plays an important role independent of social factors.
- Published
- 2024
- Full Text
- View/download PDF
33. Ambient air temperature exposure and foetal size and growth in three European birth cohorts.
- Author
-
Essers E, Granés L, Delaney S, Ballester J, Santos S, Petricola S, Yang TC, Fernández-Somoano A, Bereziartua A, Ballester F, Tardón A, Vrijheid M, Lertxundi A, McEachan RRC, El Marroun H, Tiemeier H, Iñiguez C, and Guxens M
- Subjects
- Humans, Female, Pregnancy, Adult, Temperature, Birth Cohort, Cohort Studies, Netherlands, Maternal Exposure, Cold Temperature, Europe, Spain, England, Young Adult, Fetal Development
- Abstract
Introduction: Ambient air temperature may affect birth outcomes adversely, but little is known about their impact on foetal growth throughout pregnancy. We evaluated the association between temperature exposure during pregnancy and foetal size and growth in three European birth cohorts., Methods: We studied 23,408 pregnant women from the English Born in Bradford cohort, Dutch Generation R Study, and Spanish INMA Project. Using the UrbClim
TM model, weekly ambient air temperature exposure at 100x100m resolution at the mothers' residences during pregnancy was calculated. Estimated foetal weight, head circumference, and femur length at mid and late pregnancy and weight, head circumference, and length at birth were converted into standard deviation scores (SDS). Foetal growth from mid to late pregnancy was calculated (grams or centimetres/week). Cohort/region-specific distributed lag non-linear models were combined using a random-effects meta-analysis and results presented in reference to the median percentile of temperature (14 °C)., Results: Weekly temperatures ranged from -5.6 (Bradford) to 30.3 °C (INMA-Sabadell). Cold and heat exposure during weeks 1-28 were associated with a smaller and larger head circumference in late pregnancy, respectively (e.g., for 9.5 °C: -1.6 SDS [95 %CI -2.0; -0.4] and for 20.0 °C: 1.8 SDS [0.7; 2.9]). A susceptibility period from weeks 1-7 was identified for cold exposure and a smaller head circumference at late pregnancy. Cold exposure was associated with a slower head circumference growth from mid to late pregnancy (for 5.5 °C: -0.1 cm/week [-0.2; -0.04]), with a susceptibility period from weeks 4-12. No associations that survived multiple testing correction were found for other foetal or any birth outcomes., Conclusions: Cumulative exposure to cold and heat during pregnancy was associated with changes in foetal head circumference throughout gestation, with susceptibility periods for cold during the first pregnancy trimester. No associations were found at birth, suggesting potential recovery. Future research should replicate this study across different climatic regions including varying temperature profiles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
34. A half century of exploring DNA excision repair in chromatin.
- Author
-
Smerdon MJ, Wyrick JJ, and Delaney S
- Subjects
- DNA metabolism, DNA Damage, Nucleosomes genetics, Chromatin genetics, Excision Repair
- Abstract
DNA in eukaryotic cells is packaged into the compact and dynamic structure of chromatin. This packaging is a double-edged sword for DNA repair and genomic stability. Chromatin restricts the access of repair proteins to DNA lesions embedded in nucleosomes and higher order chromatin structures. However, chromatin also serves as a signaling platform in which post-translational modifications of histones and other chromatin-bound proteins promote lesion recognition and repair. Similarly, chromatin modulates the formation of DNA damage, promoting or suppressing lesion formation depending on the chromatin context. Therefore, the modulation of DNA damage and its repair in chromatin is crucial to our understanding of the fate of potentially mutagenic and carcinogenic lesions in DNA. Here, we survey many of the landmark findings on DNA damage and repair in chromatin over the last 50 years (i.e., since the beginning of this field), focusing on excision repair, the first repair mechanism studied in the chromatin landscape. For example, we highlight how the impact of chromatin on these processes explains the distinct patterns of somatic mutations observed in cancer genomes., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
35. Molecular Imaging, Radiochemistry, and Environmental Pollutants.
- Author
-
Delaney S, Sebastiano J, Zeglis BM, and Keinänen OM
- Subjects
- Humans, Radiochemistry, Molecular Imaging, Environmental Pollutants analysis
- Abstract
The worldwide proliferation of persistent environmental pollutants is accelerating at an alarming rate. Not surprisingly, many of these pollutants pose a risk to human health. In this review, we examine recent literature in which molecular imaging and radiochemistry have been harnessed to study environmental pollutants. Specifically, these techniques offer unique ways to interrogate the pharmacokinetic profiles and bioaccumulation patterns of pollutants at environmentally relevant concentrations, thereby helping to determine their potential health risks., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)
- Published
- 2023
- Full Text
- View/download PDF
36. Site-selective radiolabeling using mushroom tyrosinase and the strain-promoted oxidation-controlled 1,2-quinone cycloaddition.
- Author
-
Rodriguez C, Delaney S, Sebastiano J, Sarrett SM, Cornejo MA, Thau S, Hosny MM, and Zeglis BM
- Abstract
We report the in vitro characterization and in vivo evaluation of a novel
89 Zr-labeled radioimmunoconjugate synthesized using a site-selective bioconjugation strategy based on the oxidation of tyrosinase residues exposed by the deglycosylation of the IgG and the subsequent strain-promoted oxidation-controlled 1,2-quinone cycloaddition between these amino acids and trans -cyclooctene-bearing cargoes. More specifically, we site-selectively modified a variant of the A33 antigen-targeting antibody huA33 with the chelator desferrioxamine (DFO), thereby producing an immunoconjugate (DFO-SPOCQ huA33) with equivalent antigen binding affinity to its parent immunoglobulin but attenuated affinity for the FcγRI receptor. This construct was subsequently radiolabeled with [89 Zr]Zr4+ to create a radioimmunoconjugate - [89 Zr]Zr-DFO-SPOCQ huA33 - in high yield and specific activity that exhibited excellent in vivo behavior in two murine models of human colorectal carcinoma., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)- Published
- 2023
- Full Text
- View/download PDF
37. Distinct and shared therapeutic neural mechanisms of mindfulness-based and social support stress reduction groups in adults with autism spectrum disorder.
- Author
-
Pagni BA, Hill E, Walsh MJM, Delaney S, Ogbeama D, Monahan L, Cook JR, Guerithault N, Dixon MV, Ballard L, and Braden BB
- Subjects
- Humans, Adult, Anxiety psychology, Anxiety Disorders, Stress, Psychological diagnostic imaging, Stress, Psychological therapy, Social Support, Mindfulness methods, Autism Spectrum Disorder diagnostic imaging, Autism Spectrum Disorder therapy
- Abstract
Background: Mindfulness-based stress reduction (MBSR) alleviates depression and anxiety in adults with autism spectrum disorder (ASD); however, underlying therapeutic neural mechanisms and mindfulness-specific effects have yet to be elucidated., Methods: We randomly assigned adults with ASD to MBSR or social support/education (SE). They completed questionnaires that assessed depression, anxiety, mindfulness traits, autistic traits and executive functioning abilities as well as a self-reflection functional MRI task. We used repeated-measures analysis of covariance (ANCOVA) to evaluate behavioural changes. To identify task-specific connectivity changes, we performed a generalized psychophysiological interactions (gPPI) functional connectivity (FC) analysis on regions of interest (ROIs; insula, amygdala, cingulum and prefrontal cortex [PFC]). We used Pearson correlations to explore brain-behaviour relationships., Results: Our final sample included 78 adults with ASD - 39 who received MBSR and 39 who received SE. Mindfulness-based stress reduction uniquely improved executive functioning abilities and increased mindfulness traits, whereas both MBSR and SE groups showed reductions in depression, anxiety and autistic traits. Decreases specific to MBSR in insula-thalamus FC were associated with anxiety reduction and increased mindfulness traits, including the trait "nonjudgment;" MBSR-specific decreases in PFC-posterior cingulate connectivity correlated with improved working memory. Both groups showed decreased amygdala-sensorimotor and medial-lateral PFC connectivity, which corresponded with reduced depression., Limitations: Larger sample sizes and neuropsychological evaluations are needed to replicate and extend these findings., Conclusion: Together, our findings suggest that MBSR and SE are similarly efficacious for depression, anxiety and autistic traits, whereas MBSR produced additional salutary effects related to executive functioning and mindfulness traits. Findings from gPPI identified shared and distinct therapeutic neural mechanisms, implicating the default mode and salience networks. Our results mark an early step toward the development of personalized medicine for psychiatric symptoms in ASD and offer novel neural targets for future neurostimulation research., Clinical Trial Registration: ClinicalTrials.gov identifier NCT04017793., Competing Interests: Competing interests: B. Pagni received support for article processing charges from the ASU Graduate Program Student Association’s Publication Grant. M. Walsh receives funding from the National Institute of Mental Health ( NIMH F31MH122107). M. Dixon received payment for execution of the program as part of this study. L. Ballard declares having received honoraria for facilitation of guided mind-fulness medications and educational presentations on mindfulness meditation., (© 2023 CMA Impact Inc. or its licensors.)
- Published
- 2023
- Full Text
- View/download PDF
38. Renal Denervation: A Practical Guide for Health Professionals Managing Hypertension.
- Author
-
Schmieder R, Burnier M, East C, Tsioufis K, and Delaney S
- Abstract
Growing evidence demonstrates the suitability of renal denervation in a broad population of patients; however, questions remain over its suitability and practical implementation. Given the rapidity of emerging data, this has been a challenging field for potential adopters to navigate. The purpose of this article is twofold: to provide navigation through emerging clinical data and evolving guidance; and to provide physicians with practical, evidence-based advice for identifying eligible patients and providing appropriate management in the pre- and postintervention settings. Although many of these recommendations are based on existing published guidance documents, we reflect equally on our own experiences of using this technology., Competing Interests: Disclosure: RS has received fees from Medtronic, Recor and Ablation Solutions. MB has received fees from Servier International, Menarini, Cincor, Idorsia and Bayer. CE has received fees from Medtronic Vascular and is on the Radcliffe Group Advisory Board. KT has received fees from Medtronic, Abbott, Bayer, Novartis, AstraZeneca, Boehringer, Pfizer, Mylan, Chiesi, Pharmanel, Sanofi, Vianex, Winmedica and Elpen. SD is an employee of Radcliffe Medical Media., (Copyright © The Author(s), 2023. Published by Radcliffe Group Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
39. Quaternary glucocorticoid receptor structure highlights allosteric interdomain communication.
- Author
-
Postel S, Wissler L, Johansson CA, Gunnarsson A, Gordon E, Collins B, Castaldo M, Köhler C, Öling D, Johansson P, Fröderberg Roth L, Beinsteiner B, Dainty I, Delaney S, Klaholz BP, Billas IML, and Edman K
- Subjects
- Humans, Ligands, Gene Expression Regulation, DNA metabolism, Receptors, Glucocorticoid chemistry, Receptors, Glucocorticoid genetics, Receptors, Glucocorticoid metabolism, Transcription Factors metabolism
- Abstract
The glucocorticoid receptor (GR) is a ligand-activated transcription factor that binds DNA and assembles co-regulator complexes to regulate gene transcription. GR agonists are widely prescribed to people with inflammatory and autoimmune diseases. Here we present high-resolution, multidomain structures of GR in complex with ligand, DNA and co-regulator peptide. The structures reveal how the receptor forms an asymmetric dimer on the DNA and provide a detailed view of the domain interactions within and across the two monomers. Hydrogen-deuterium exchange and DNA-binding experiments demonstrate that ligand-dependent structural changes are communicated across the different domains in the full-length receptor. This study demonstrates how GR forms a distinct architecture on DNA and how signal transmission can be modulated by the ligand pharmacophore, provides a platform to build a new level of understanding of how receptor modifications can drive disease progression and offers key insight for future drug design., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2023
- Full Text
- View/download PDF
40. Adolescent Psychological Assets and Cardiometabolic Health Maintenance in Adulthood: Implications for Health Equity.
- Author
-
Qureshi F, Guimond AJ, Tsao E, Delaney S, Boehm JK, and Kubzansky LD
- Subjects
- Humans, Adolescent, Female, Adult, Male, Longitudinal Studies, Ethnicity, Biomarkers, Health Equity, Cardiovascular Diseases epidemiology
- Abstract
Background Positive cardiometabolic health (CMH) is defined as meeting recommended levels of multiple cardiometabolic risk factors in the absence of manifest disease. Prior work finds that few individuals-particularly members of minoritized racial and ethnic groups-meet these criteria. This study investigated whether psychological assets help adolescents sustain CMH in adulthood and explored interactions by race and ethnicity. Methods and Results Participants were 3478 individuals in the National Longitudinal Study of Adolescent Health (49% female; 67% White, 15% Black, 11% Latinx, 6% other [Native American, Asian, or not specified]). In Wave 1 (1994-1995; mean age=16 years), data on 5 psychological assets (optimism, happiness, self-esteem, belongingness, and feeling loved) were used to create a composite asset index (range=0-5). In Waves 4 (2008; mean age=28 years) and 5 (2016-2018; mean age=38 years), CMH was defined using 7 clinically assessed biomarkers. Participants with healthy levels of ≥6 biomarkers at Waves 4 and 5 were classified as maintaining CMH over time. The prevalence of CMH maintenance was 12%. Having more psychological assets was associated with better health in adulthood (odds ratio [OR]
linear trend , 1.12 [95% CI, 1.01-1.25]). Subgroup analyses found substantive associations only among Black participants (OR, 1.35 [95% CI, 1.00-1.82]). Additionally, there was some evidence that racial and ethnic disparities in CMH maintenance may be less pronounced among participants with more assets. Conclusions Youth with more psychological assets were more likely to experience favorable CMH patterns 2 decades later. The strongest associations were observed among Black individuals. Fostering psychological assets in adolescence may help prevent cardiovascular disease and play an underappreciated role in shaping health inequities.- Published
- 2023
- Full Text
- View/download PDF
41. Sex-related brain connectivity correlates of compensation in adults with autism: insights into female protection.
- Author
-
Walsh MJM, Pagni B, Monahan L, Delaney S, Smith CJ, Baxter L, and Braden BB
- Subjects
- Male, Adult, Humans, Female, Magnetic Resonance Imaging methods, Brain diagnostic imaging, Brain Mapping methods, Neural Pathways diagnostic imaging, Autistic Disorder, Autism Spectrum Disorder diagnostic imaging
- Abstract
The male preponderance in autism spectrum disorder (ASD) led to the hypothesis that aspects of female biology are protective against ASD. Females with ASD (ASD-F) report more compensatory behaviors (i.e. "camouflaging") to overcome ASD-related social differences, which may be a mechanism of protection. No studies have examined sex-related brain pathways supporting camouflaging in ASD-F, despite its potential to inform mechanisms underlying the ASD sex bias. We used functional connectivity (FC) to investigate "sex-atypical" and "sex-typical" FC patterns linked to camouflaging in adults with ASD and examined multimodal coherence of findings via structural connectometry. Exploratory associations with cognitive/emotional functioning examined the adaptive nature of FC patterns. We found (i) "sex-atypical" FC patterns linked to camouflaging in the hypothalamus and precuneus and (ii) "sex-typical" patterns in the right anterior cingulate and anterior parahippocampus. Higher hypothalamic FC with a limbic reward cluster also correlated with better cognitive control/emotion recognition. Structural connectometry validated FC results with consistent brain pathways/effect patterns implicated in ASD-F. In summary, "male-typical" and "female-typical" brain connectivity patterns support camouflaging in ASD-F in circuits implicated in reward, emotion, and memory retrieval. "Sex-atypical" results are consistent with fetal steroidogenic/neuroinflammatory hypotheses. However, female genetics/biology may contribute to "female-typical" patterns implicated in camouflaging., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)
- Published
- 2022
- Full Text
- View/download PDF
42. Antibody Engineering for Nuclear Imaging and Radioimmunotherapy.
- Author
-
Rodriguez C, Delaney S, Sarrett SM, Keinänen OM, and Zeglis BM
- Subjects
- Antibodies, Molecular Imaging methods, Radiopharmaceuticals therapeutic use, Immunoconjugates therapeutic use, Radioimmunotherapy methods
- Abstract
Radiolabeled antibodies have become indispensable tools in nuclear medicine. However, the natural roles of antibodies within the immune system mean that they have several intrinsic limitations as a platform for radiopharmaceuticals. In recent years, the field has increasingly turned to antibody engineering to circumvent these issues while retaining the manifold benefits of the immunoglobulin framework. In this "Focus on Molecular Imaging" review, we cover recent advances in the application of antibody engineering to immunoPET, immunoSPECT, and radioimmunotherapy. Specifically, we address how antibody engineering has been used to improve radioimmunoconjugates on four fronts: optimizing pharmacokinetics, facilitating site-specific bioconjugation, modulating Fc interactions, and creating bispecific constructs., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)
- Published
- 2022
- Full Text
- View/download PDF
43. Formative Research to Inform Market-Based Interventions to Increase Egg Purchase and Consumption in Tigray, Ethiopia.
- Author
-
McClung S, Delaney S, Aakesson A, Baye K, Klein A, Mowl Z, and Clemmons L
- Subjects
- Animals, Ethiopia, Food Supply, Humans, Pilot Projects, Diet, Eggs
- Abstract
Animal source foods (ASFs) have a demonstrated ability to improve child health yet are underutilized by many communities faced with malnutrition. Recognizing that improving knowledge about the benefits of consuming ASFs alone is not adequate to change behavior, the Studying Animal Food Markets in Rural Areas (SAFIRA) pilot project planned to test a market-based intervention to increasing the intake of ASFs by children 6-23 months in rural Tigray, Ethiopia. Our process of designing in-market behavior change strategies involved identifying the project's target ASF, cocreating and testing marketing interventions, and understanding barriers and enablers driving key retailer behaviors. Qualitative research methods including focus group discussions, key informant interviews, trials of improved practices, and transect walks were used throughout 2 rounds of formative research. The first round of formative research led the project to focus on eggs, and the second round resulted in an improved understanding of the Tigrayan local food markets and egg consumption. Consumers were receptive to nutrition messaging from trusted community members and consider eggs to be healthy and affordable relative to other ASFs. Despite a willingness on the part of egg retailers in Tigrayan markets to try new practices to market eggs to consumers, formative research revealed that retailers function primarily as aggregators, moving eggs toward urban markets, correcting a foundational assumption that households routinely purchase eggs at local markets. These findings demonstrate the importance of formative research to inform design-especially in the development of context-specific behavior change interventions situated within local marketplaces., (© McClung et al.)
- Published
- 2022
- Full Text
- View/download PDF
44. Shooting hoops: globetrotting plasmids spreading more than just antimicrobial resistance genes across One Health.
- Author
-
Smyth C, Leigh RJ, Delaney S, Murphy RA, and Walsh F
- Subjects
- Animals, Anti-Bacterial Agents pharmacology, Drug Resistance, Bacterial genetics, Humans, Plasmids genetics, Anti-Infective Agents, One Health
- Abstract
Our study provides novel insights into the global nature of antimicrobial resistance (AMR) plasmids across the food chain. We provide compelling evidence of the globetrotting nature of AMR plasmids and the need for surveillance to sequence plasmids with a template of analyses for others to expand these data. The AMR plasmids analysed were detected in 63 countries and in samples from humans, animals and the environment. They contained a combination of known and novel AMR genes, metal resistance genes, virulence factors, phage and replicon types.
- Published
- 2022
- Full Text
- View/download PDF
45. Pregnancy Care for Patients With Super Morbid Obesity.
- Author
-
Olerich K, Soper D, Delaney S, and Sterrett M
- Abstract
The patient with obesity represents unique challenges to the medical community and, in the setting of pregnancy, additional risks to both mother and fetus. This document will focus on the risks and considerations needed to care for the women with obesity and her fetus during the antepartum, intrapartum, and immediate postpartum stages of pregnancy. Specific attention will be given to pregnancy in the setting of class III and super morbid obesity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Olerich, Soper, Delaney and Sterrett.)
- Published
- 2022
- Full Text
- View/download PDF
46. Legionella water testing and the EU Drinking Water Directive: could potentially harmful Legionella bacteria slip through the gaps?
- Author
-
Delaney S, Arcari T, and O'Connor O
- Subjects
- Bacteria, Humans, Water Microbiology, Drinking Water, Legionella, Legionnaires' Disease
- Published
- 2022
- Full Text
- View/download PDF
47. Waitlisted and Transplant Patient Perspectives on Expanding Access to Deceased-Donor Kidney Transplant: A Qualitative Study.
- Author
-
Rosaasen C, Rosaasen N, Mainra R, Trachtenberg A, Ho J, Parsons C, Delaney S, and Mansell H
- Abstract
Background: A concerning number of kidneys (eg, expanded donor criteria, extended criteria, or marginal kidneys) are discarded yearly while patients experience significant morbidity and mortality on the transplant waitlist. Novel solutions are needed to solve the shortage of kidneys available for transplant. Patient perceptions regarding the use of these less than ideal kidneys remain unexplored., Objective: To explore the perspectives of patients who have previously received a less than ideal kidney in the past and patients awaiting transplant who could potentially benefit from one., Design: Qualitative description study., Setting: 2 provinces in Canada participated (Saskatchewan and Manitoba)., Patients: Patients with end-stage kidney disease who were awaiting kidney transplant and were either (a) aged 65 years and older, or (b) 55 years and older with other medical conditions (eg, diabetes)., Methods: Criterion sampling was used to identify participants. Semi-structured, one-on-one interviews were conducted virtually, which explored perceived quality of life, perceptions of less than ideal kidneys, risk tolerance for accepting one, and educational needs to make such a choice. The interviews were transcribed verbatim and thematic analysis was used to analyze the data., Results: 15 interviews were conducted with usable data (n = 10 pretransplant; n = 5 posttransplant). Participants were a mean of 65.5 ± 8.8 years old. Four interrelated themes became prominent including (1) patient awareness and understanding of their situation or context, (2) a desire for information, (3) a desire for freedom from dialysis, and (4) trust. Subthemes of transparency, clarity, standardization, and autonomy were deemed important for participant education. The majority of pretransplant participants (n = 8/10) indicated that between 3 and 5 years off of dialysis would make the risk of accepting a less than ideal kidney feel worthwhile., Limitation: The study setting was limited to 2 Canadian provinces, which limits the generalizability. Furthermore, the participants were homogenous in demographics such as ethnicity., Conclusion: These findings indicate that patients are comfortable to accept a less than ideal kidney for transplant in situations where their autonomy is respected, they are provided clear, standardized, and transparent information, and when they trust their physician. These results will be used to inform the development of a new national registry for expanding access to deceased-donor kidney transplant., Trial Registration: Not registered., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: C.R. received payment from Canadian Blood Services as a summer student to complete the study; N.R., A.T., and S.D. report no conflicts of interest; R.M. is the Chair-Kidney Transplant Advisory Committee; J.H. has received funding from the Canadian Institutes for Health Research and Canada Foundation for Innovation, received support for travel from the Transplant Manitoba Adult Kidney Program, was Vice-Chair of the Institute Advisory Board for Canadian Institutes for Health Research, Institute for Nutrition, Metabolism and Diabetes, Scientific Co-Chair, Canadian Transplant Summit 2019, Banff Canada for the Canadian Society of Transplantation, Editorial Board, Canadian Journal of Kidney Health and Disease, Guest Editor, Frontiers in Immunology and received assay reagents from Thermo Fisher Scientific and Echelon Biosciences. None of these activities are related to the work in this manuscript; C.P. received support from Canadian Blood Services for meetings to arrange this project; H.M. received support from Canadian Blood Services to conduct this research. She also received funding from the Respiratory Research Center and a speaker honorarium from Astra Zeneca for work unrelated to this project., (© The Author(s) 2022.)
- Published
- 2022
- Full Text
- View/download PDF
48. Platelet Biomarkers in Patients with Atherosclerotic Extracranial Carotid Artery Stenosis: A Systematic Review.
- Author
-
Subramanian A, Delaney S, Murphy SJX, Smith DR, Offiah C, McMahon J, de Borst GJ, Naylor AR, Hamilton G, Kinsella JA, and McCabe DJH
- Subjects
- Aspirin therapeutic use, Biomarkers, Blood Platelets, Humans, Platelet Aggregation Inhibitors therapeutic use, Carotid Stenosis complications, Carotid Stenosis diagnostic imaging, Carotid Stenosis drug therapy, Stroke etiology
- Abstract
Objective: The aim was to enhance understanding of the role of platelet biomarkers in the pathogenesis of vascular events and risk stratifying patients with asymptomatic or symptomatic atherosclerotic carotid stenosis., Data Sources: Systematic review conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement., Review Methods: A systematic review collated data from 1975 to 2020 on ex vivo platelet activation and platelet function/reactivity in patients with atherosclerotic carotid stenosis., Results: Forty-three studies met the inclusion criteria; the majority included patients on antiplatelet therapy. Five studies showed increased platelet biomarkers in patients with ≥ 30% asymptomatic carotid stenosis (ACS) vs. controls, with one neutral study. Preliminary data from one study suggested that quantification of "coated platelets" in combination with stenosis severity may aid risk stratification in patients with ≥ 50% - 99% ACS. Platelets were excessively activated in patients with ≥ 30% symptomatic carotid stenosis (SCS) vs. controls (≥ 11 positive studies and one neutral study). Antiplatelet-High on Treatment Platelet Reactivity (HTPR), previously called "antiplatelet resistance", was observed in 23% - 57% of patients on aspirin, with clopidogrel-HTPR in 25% - 100% of patients with ≥ 50% - 99% ACS. Aspirin-HTPR was noted in 9.5% - 64% and clopidogrel-HTPR in 0 - 83% of patients with ≥ 50% SCS. However, the data do not currently support the use of ex vivo platelet function/reactivity testing to tailor antiplatelet therapy outside of a research setting. Platelets are excessively activated (n = 5), with increased platelet counts (n = 3) in recently symptomatic vs. asymptomatic patients, including those without micro-emboli on transcranial Doppler (TCD) monitoring (n = 2). Most available studies (n = 7) showed that platelets become more reactive or activated following carotid endarterectomy or stenting, either as an acute phase response to intervention or peri-procedural treatment., Conclusion: Platelets are excessively activated in patients with carotid stenosis vs. controls, in recently symptomatic vs. asymptomatic patients, and may become activated/hyper-reactive following carotid interventions despite commonly prescribed antiplatelet regimens. Further prospective multicentre studies are required to determine whether models combining clinical, neurovascular imaging, and platelet biomarker data can facilitate optimised antiplatelet therapy in individual patients with carotid stenosis., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
49. Xylazine detected in unregulated opioids and drug administration equipment in Toronto, Canada: clinical and social implications.
- Author
-
Bowles JM, McDonald K, Maghsoudi N, Thompson H, Stefan C, Beriault DR, Delaney S, Wong E, and Werb D
- Subjects
- Analgesics, Opioid, Canada, Fentanyl, Humans, Xylazine, Drug Overdose, Illicit Drugs, Pharmaceutical Preparations
- Abstract
Background: The North American opioid overdose crisis is driven in large part by the presence of unknown psychoactive adulterants in the dynamic, unregulated drug supply. We herein report the first detection of the psychoactive veterinary compound xylazine in Toronto, the largest urban center in Canada, by the city's drug checking service., Methods: Toronto's Drug Checking Service launched in October 2019. Between then and February 2021, 2263 samples were submitted for analysis. The service is offered voluntarily at harm reduction agencies that include supervised consumption services. Samples were analyzed using gas chromatography-mass spectrometry or liquid chromatography-high resolution mass spectrometry. Targeted and/or untargeted screens for psychoactive substances were undertaken., Results: In September 2020, xylazine was first detected by Toronto's Drug Checking Service. Among samples analyzed from September 2020 to February 2021 expected to contain fentanyl in isolation (610) or in combination with methamphetamine (16), xylazine was detected in 46 samples (7.2% and 12.5% of samples, respectively). Samples were predominantly drawn from used drug equipment. Three of the samples containing xylazine (6.5%) were associated with an overdose., Conclusion: We present the first detection of xylazine in Toronto, North America's fourth-largest metropolitan area. The increased risk of overdose associated with use of xylazine and its detection within our setting highlights the importance of drug checking services in supporting rapid responses to the emergence of potentially harmful adulterants. These data also highlight the clinical challenges presented by the dynamic nature of unregulated drug markets and the concomitant need to establish regulatory structures to reduce their contribution to overdose morbidity and mortality., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
50. Finding the source of intoxication: better salicylate than never.
- Author
-
Aga Z, Matthews N, Delaney S, Wong N, Poley R, and Perl J
- Subjects
- Salicylates
- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.