36 results on '"Nicholas Han"'
Search Results
2. Signaling Through FcγRIIA and the C5a-C5aR Pathway Mediate Platelet Hyperactivation in COVID-19
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Sokratis A. Apostolidis, Amrita Sarkar, Heather M. Giannini, Rishi R. Goel, Divij Mathew, Aae Suzuki, Amy E. Baxter, Allison R. Greenplate, Cécile Alanio, Mohamed Abdel-Hakeem, Derek A. Oldridge, Josephine R. Giles, Jennifer E. Wu, Zeyu Chen, Yinghui Jane Huang, Jonathan Belman, Ajinkya Pattekar, Sasikanth Manne, Oliva Kuthuru, Jeanette Dougherty, Brittany Weiderhold, Ariel R. Weisman, Caroline A. G. Ittner, Sigrid Gouma, Debora Dunbar, Ian Frank, Alexander C. Huang, Laura A. Vella, The UPenn COVID Processing Unit, John P. Reilly, Scott E. Hensley, Lubica Rauova, Liang Zhao, Nuala J. Meyer, Mortimer Poncz, Charles S. Abrams, E. John Wherry, Sharon Adamski, Zahidul Alam, Mary M. Addison, Katelyn T. Byrne, Aditi Chandra, Hélène C. Descamps, Nicholas Han, Yaroslav Kaminskiy, Shane C. Kammerman, Justin Kim, Jacob T. Hamilton, Nune Markosyan, Julia Han Noll, Dalia K. Omran, Eric Perkey, Elizabeth M. Prager, Dana Pueschl, Austin Rennels, Jennifer B. Shah, Jake S. Shilan, Nils Wilhausen, and Ashley N. Vanderbeck more...
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platelet ,COVID - 19 ,FcγRIIa ,complement ,fostamatinib ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Patients with COVID-19 present with a wide variety of clinical manifestations. Thromboembolic events constitute a significant cause of morbidity and mortality in patients infected with SARS-CoV-2. Severe COVID-19 has been associated with hyperinflammation and pre-existing cardiovascular disease. Platelets are important mediators and sensors of inflammation and are directly affected by cardiovascular stressors. In this report, we found that platelets from severely ill, hospitalized COVID-19 patients exhibited higher basal levels of activation measured by P-selectin surface expression and had poor functional reserve upon in vitro stimulation. To investigate this question in more detail, we developed an assay to assess the capacity of plasma from COVID-19 patients to activate platelets from healthy donors. Platelet activation was a common feature of plasma from COVID-19 patients and correlated with key measures of clinical outcome including kidney and liver injury, and APACHEIII scores. Further, we identified ferritin as a pivotal clinical marker associated with platelet hyperactivation. The COVID-19 plasma-mediated effect on control platelets was highest for patients that subsequently developed inpatient thrombotic events. Proteomic analysis of plasma from COVID-19 patients identified key mediators of inflammation and cardiovascular disease that positively correlated with in vitro platelet activation. Mechanistically, blocking the signaling of the FcγRIIa-Syk and C5a-C5aR pathways on platelets, using antibody-mediated neutralization, IgG depletion or the Syk inhibitor fostamatinib, reversed this hyperactivity driven by COVID-19 plasma and prevented platelet aggregation in endothelial microfluidic chamber conditions. These data identified these potentially actionable pathways as central for platelet activation and/or vascular complications and clinical outcomes in COVID-19 patients. In conclusion, we reveal a key role of platelet-mediated immunothrombosis in COVID-19 and identify distinct, clinically relevant, targetable signaling pathways that mediate this effect. more...
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- 2022
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3. CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer
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Divij Mathew, Laura A. Vella, Randall A. Oyer, Jedd D. Wolchok, James Robinson, Cécile Alanio, Susan DeWolf, Kara N. Maxwell, Amy E. Baxter, Erin Bange, Karan Naik, Scott E. Hensley, Justin Kim, Anita Kumar, Tara Perloff, Adam J Widman, Madison E. Weirick, Santosha Vardhana, Madeline A Hwee, Florence Porterfield, Derek A. Oldridge, Krista R Budzik, Samuel J Kerr, Justine V. Cohen, Nicholas Han, Josephine R. Giles, Christopher M McAllister, Ariel R. Weisman, Michael Galantino, Angela DeMichele, Ivan Maillard, Charlotte Roberts, Caroline A. G. Ittner, Paul Wileyto, Ronac Mamtani, Lova Sun, Susan Tollett, Jennifer E. Wu, Olutosin Owoyemi, Sharon Adamski, John P. Reilly, Alexander C. Huang, Sigrid Gouma, Ryan Massa, Allison R. Greenplate, Sawsan R. Boutemine, E. John Wherry, Heather M. Giannini, Tiffanie K. Jones, Carla Wright, Olutwatosin Oniyide, Emily M. Kugler, N. Esther Babady, Alfred L. Garfall, Peter Maslak, Robert H. Vonderheide, Cathy Zheng, R.S. Agyekum, Nuala J. Meyer, and Thomas G. Dunn more...
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0301 basic medicine ,biology ,business.industry ,T cell ,Cancer ,General Medicine ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Humoral immunity ,Immunology ,biology.protein ,medicine ,Cytotoxic T cell ,Antibody ,Prospective cohort study ,business ,Survival rate - Abstract
Patients with cancer have high mortality from coronavirus disease 2019 (COVID-19), and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 patients with cancer who were hospitalized for COVID-19, patients with hematologic cancer had higher mortality relative to patients with solid cancer. In two additional cohorts, flow cytometric and serologic analyses demonstrated that patients with solid cancer and patients without cancer had a similar immune phenotype during acute COVID-19, whereas patients with hematologic cancer had impairment of B cells and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses. Despite the impaired humoral immunity and high mortality in patients with hematologic cancer who also have COVID-19, those with a greater number of CD8 T cells had improved survival, including those treated with anti-CD20 therapy. Furthermore, 77% of patients with hematologic cancer had detectable SARS-CoV-2-specific T cell responses. Thus, CD8 T cells might influence recovery from COVID-19 when humoral immunity is deficient. These observations suggest that CD8 T cell responses to vaccination might provide protection in patients with hematologic cancer even in the setting of limited humoral responses. more...
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- 2021
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4. Ketogenic Diet‐Associated Worsening of Osteoarthritis Histologic Secerity, Increased Pain Sensitivity and Gut Microbiome Dysbiosis in Mice
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Gabby Dyson, Montana Barrett, Leoni Schlupp, Emmaline Prinz, Nicholas Hannebut, Aleksander Szymczak, Cindy Miranda Brawner, and Matlock A. Jeffries
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
Objectives Dietary interventions are a potentially powerful treatment option for knee osteoarthritis (OA). The objective of this study was to evaluate a well‐formulated ketogenic diet (KD) in the context of knee OA histology and pain using the destabilization of the medial meniscus (DMM) mouse model and correlate with gut microbiome and systemic cytokine levels. Methods Adult male mice underwent unilateral DMM or sham surgery and were then fed eight weeks of KD or chow. At baseline and every two weeks, mechanical allodynia of the operated and contralateral knees was assessed via analgesiometry. Knee joints were collected for histology, gut microbiome analysis was performed on cecal material via 16S sequencing, and serum cytokines were analyzed via Bio‐Plex assay. Results KD mice had worse histopathologic OA after DMM (mean ± SEM Osteoarthritis Research Society International score: KD‐DMM: 4.0 ± 0.5 vs chow‐DMM: 2.7 ± 0.08; P = 0.02). KD mice had increased mechanical allodynia postsurgery (P = 0.005 in mixed‐effects model). The gut microbiome changed substantially with KD: 59 clades were altered by KD in DMM and 39 by KD in sham (36 were shared, 25 overlapped with previous murine OA studies). Several clades were correlated on an individual‐mouse level with both histology and allodynia (eg, Lactobacillus histology P = 0.004, allodynia P = 1 × 10−4). Serum analysis showed four cytokines increased with KD (interleukin [IL]‐1β, IL‐2, IL‐3, and IL‐13). Conclusion KD started immediately after OA induction via DMM is associated with worsened histologic outcomes. KD also worsens mechanical allodynia after either DMM or sham surgery. KD induces significant gut microbiome dysbiosis in clades previously associated with murine OA. more...
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- 2025
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5. mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern
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Moses Awofolaju, Amy E. Baxter, Ajinkya Pattekar, J. Han Noll, Derek A. Oldridge, Ian Frank, Alessandro Sette, E. John Wherry, Paul Bates, Daniela Weiskopf, Eline T. Luning Prak, Elizabeth M Drapeau, Oliva Kuthuru, Michael R. Betts, M. M. Addison, Alba Grifoni, S. C. Kammerman, Justine C. Williams, Sokratis A. Apostolidis, Rishi R. Goel, H. C. Descamps, Kendall A. Lundgreen, Scott E. Hensley, J. T. Hamilton, Sherea Long, E. M. Prager, Laura A. Vella, Justin Kim, Nicholas Han, Jacob T. Hamilton, Y. Kaminskiy, Leticia Kuri-Cervantes, D. Pueschl, Josephine R. Giles, Z. Alam, Christopher M McAllister, A. Rennels, Divij Mathew, Nicole Tanenbaum, Sarah Herring, Kurt D'Andrea, Aaron M. Rosenfeld, D. K. Omran, Philip Hicks, Jeanette Dougherty, Maura McLaughlin, N. Markosyan, J. S. Shilan, A. N. Vanderbeck, A. Pattekar, David S. Khoury, Allison R. Greenplate, Miles P. Davenport, A. Chandra, K. T. Byrne, Madison E. Weirick, A. R. Greenplate, Sigrid Gouma, Mark M Painter, Sarah Dysinger, Harsh Sharma, Amanda Hicks, J. B. Shah, Arnold Reynaldi, N. Wilhausen, Wenzhao Meng, Sharon Adamski, S. Adamski, Scott Korte, and E. Perkey more...
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Messenger RNA ,COVID-19 Vaccines ,Multidisciplinary ,SARS-CoV-2 ,T cell ,Alpha (ethology) ,biochemical phenomena, metabolism, and nutrition ,Biology ,Article ,Vaccination ,medicine.anatomical_structure ,Immunity ,Immunology ,Humoral immunity ,medicine ,biology.protein ,Humans ,mRNA Vaccines ,Antibody ,Immunologic Memory ,CD8 - Abstract
SARS-CoV-2 mRNA vaccines have shown remarkable efficacy, especially in preventing severe illness and hospitalization. However, the emergence of several variants of concern and reports of declining antibody levels have raised uncertainty about the durability of immune memory following vaccination. In this study, we longitudinally profiled both antibody and cellular immune responses in SARS-CoV-2 naïve and recovered individuals from pre-vaccine baseline to 6 months post-mRNA vaccination. Antibody and neutralizing titers decayed from peak levels but remained detectable in all subjects at 6 months post-vaccination. Functional memory B cell responses, including those specific for the receptor binding domain (RBD) of the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants, were also efficiently generated by mRNA vaccination and continued to increase in frequency between 3 and 6 months post-vaccination. Notably, most memory B cells induced by mRNA vaccines were capable of cross-binding variants of concern, and B cell receptor sequencing revealed significantly more hypermutation in these RBD variant-binding clones compared to clones that exclusively bound wild-type RBD. Moreover, the percent of variant cross-binding memory B cells was higher in vaccinees than individuals who recovered from mild COVID-19. mRNA vaccination also generated antigen-specific CD8+ T cells and durable memory CD4+ T cells in most individuals, with early CD4+ T cell responses correlating with humoral immunity at later timepoints. These findings demonstrate robust, multi-component humoral and cellular immune memory to SARS-CoV-2 and current variants of concern for at least 6 months after mRNA vaccination. Finally, we observed that boosting of pre-existing immunity with mRNA vaccination in SARS-CoV-2 recovered individuals primarily increased antibody responses in the short-term without significantly altering antibody decay rates or long-term B and T cell memory. Together, this study provides insights into the generation and evolution of vaccine-induced immunity to SARS-CoV-2, including variants of concern, and has implications for future booster strategies. more...
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- 2021
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6. CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer
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Lova Sun, Derek A. Oldridge, Thomas G. Dunn, M. Galantino, Ronac Mamtani, T. Perloff, Anita Kumar, Nicholas Han, Nuala J. Meyer, Peter Maslak, C. Roberts, Santosha Vardhana, Ariel R. Weisman, Caroline A. G. Ittner, Adam J Widman, Randall A. Oyer, E. Wherry, S. Kerr, Divij Mathew, Angela DeMichele, Christopher M McAllister, Amy E. Baxter, Ivan Maillard, C. Wright, Jedd D. Wolchok, James Robinson, Justine V. Cohen, Cécile Alanio, Susan DeWolf, Allison R. Greenplate, K. Budzik, Kara N. Maxwell, Scott E. Hensley, N. E. Babady, Josephine R. Giles, Madison E. Weirick, Justin Kim, K. Naik, Sawsan R. Boutemine, Laura A. Vella, Sharon Adamski, Jennifer E. Wu, Florence Porterfield, Alexander C. Huang, Ryan Massa, S. Tollett, Alfred L. Garfall, Sigrid Gouma, Emily M. Kugler, Heather M. Giannini, Tiffanie K. Jones, Oluwatosin Oniyide, John P. Reilly, Erin Bange, R.S. Agyekum, E. P. Wileyto, Olutosin Owoyemi, Robert H. Vonderheide, and Cathy Zheng more...
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business.industry ,Cancer ,medicine.disease ,Serology ,Immune system ,medicine.anatomical_structure ,Humoral immunity ,Cohort ,Immunology ,Medicine ,Cytotoxic T cell ,business ,Viral load ,B cell - Abstract
Cancer patients have increased morbidity and mortality from Coronavirus Disease 2019 (COVID-19), but the underlying immune mechanisms are unknown. In a cohort of 100 cancer patients hospitalized for COVID-19 at the University of Pennsylvania Health System, we found that patients with hematologic cancers had a significantly higher mortality relative to patients with solid cancers after accounting for confounders including ECOG performance status and active cancer status. We performed flow cytometric and serologic analyses of 106 cancer patients and 113 non-cancer controls from two additional cohorts at Penn and Memorial Sloan Kettering Cancer Center. Patients with solid cancers exhibited an immune phenotype similar to non-cancer patients during acute COVID-19 whereas patients with hematologic cancers had significant impairment of B cells and SARS-CoV-2-specific antibody responses. High dimensional analysis of flow cytometric data revealed 5 distinct immune phenotypes. An immune phenotype characterized by CD8 T cell depletion was associated with a high viral load and the highest mortality of 71%, among all cancer patients. In contrast, despite impaired B cell responses, patients with hematologic cancers and preserved CD8 T cells had a lower viral load and mortality. These data highlight the importance of CD8 T cells in acute COVID-19, particularly in the setting of impaired humoral immunity. Further, depletion of B cells with anti-CD20 therapy resulted in almost complete abrogation of SARS-CoV-2-specific IgG and IgM antibodies, but was not associated with increased mortality compared to other hematologic cancers, when adequate CD8 T cells were present. Finally, higher CD8 T cell counts were associated with improved overall survival in patients with hematologic cancers. Thus, CD8 T cells likely compensate for deficient humoral immunity and influence clinical recovery of COVID-19. These observations have important implications for cancer and COVID-19-directed treatments, immunosuppressive therapies, and for understanding the role of B and T cells in acute COVID-19. more...
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- 2021
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7. Comprehensive mapping of immune perturbations associated with severe COVID-19
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Laura A. Vella, Madison E. Weirick, Ajinkya Pattekar, Luanne Bershaw, Ariel R. Weisman, Claudia P. Arevalo, Michael R. Betts, Nicholas Han, Leticia Kuri-Cervantes, Marcus J. Bolton, Divij Mathew, Sigrid Gouma, Eline T. Luning Prak, Scott E. Hensley, Wenzhao Meng, Caroline A. G. Ittner, Justin Kim, Eileen C. Goodwin, Allison R. Greenplate, Jeanette Dougherty, E. John Wherry, Amy E. Baxter, Tiffanie K. Jones, Oliva Kuthuru, Aaron M. Rosenfeld, Nuala J. Meyer, R.S. Agyekum, Nilam S. Mangalmurti, M. Betina Pampena, Elizabeth M. Anderson, and Sokratis A. Apostolidis more...
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Male ,0301 basic medicine ,Coronavirus disease 2019 (COVID-19) ,Neutrophils ,T-Lymphocytes ,T cell ,Pneumonia, Viral ,Immunology ,B-Lymphocyte Subsets ,macromolecular substances ,Lymphocyte Activation ,Betacoronavirus ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Immunity ,Humans ,Medicine ,Lymphocyte Count ,Neutrophil to lymphocyte ratio ,Clonal Selection, Antigen-Mediated ,Receptor ,Pandemics ,Research Articles ,Aged ,SARS-CoV-2 ,business.industry ,R-Articles ,COVID-19 ,General Medicine ,Middle Aged ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Immunity, Innate ,Coronavirus ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cytokines ,Female ,Coronavirus Infections ,business ,Immunologic Memory ,Pneumonia (non-human) ,Clonal selection - Abstract
Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified extensive induction and activation of multiple immune lineages, including T cell activation, oligoclonal plasmablast expansion, and Fc and trafficking receptor modulation on innate lymphocytes and granulocytes, that distinguished severe COVID-19 cases from healthy donors or SARS-CoV-2-recovered or moderate severity patients. We found the neutrophil to lymphocyte ratio to be a prognostic biomarker of disease severity and organ failure. Our findings demonstrate broad innate and adaptive leukocyte perturbations that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation., Profound plasmablast expansion, innate cell modulation, and T cell activation are defining features of severe COVID-19. more...
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- 2020
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8. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications
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Ariel R. Weisman, Ajinkya Pattekar, Fang Chen, Caroline A. G. Ittner, Cécile Alanio, Sasikanth Manne, Zeyu Chen, E. John Wherry, Holly Ramage, M. Betina Pampena, Scott E. Hensley, Kito Nzingha, Justin Kim, Amy E. Baxter, Jeanette Dougherty, Divij Mathew, Michael R. Betts, Allison R. Greenplate, Claudia P. Arevalo, Yinghui Jane Huang, Leticia Kuri-Cervantes, Josephine R. Giles, Derek A. Oldridge, Nuala J. Meyer, Jennifer E. Wu, Marcus J. Bolton, Laura A. Vella, John P. Reilly, Alexander C. Huang, Elizabeth M. Anderson, Eileen C. Goodwin, Madison E. Weirick, Simon F. Lacey, Sokratis A. Apostolidis, Sara Cherry, Kurt D'Andrea, Nicholas Han, Sigrid Gouma, and Oliva Kuthuru more...
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Multidisciplinary ,biology ,business.industry ,R-Articles ,T cell ,Immunology ,Acquired immune system ,Virus ,medicine.anatomical_structure ,Immune system ,biology.protein ,Medicine ,Antibody ,business ,Cytometry ,Research Articles ,B-Lymphocyte Subsets ,B cell ,Research Article - Abstract
Immune profiling of COVID-19 patients Coronavirus disease 2019 (COVID-19) has affected millions of people globally, yet how the human immune system responds to and influences COVID-19 severity remains unclear. Mathew et al. present a comprehensive atlas of immune modulation associated with COVID-19. They performed high-dimensional flow cytometry of hospitalized COVID-19 patients and found three prominent and distinct immunotypes that are related to disease severity and clinical parameters. Arunachalam et al. report a systems biology approach to assess the immune system of COVID-19 patients with mild-to-severe disease. These studies provide a compendium of immune cell information and roadmaps for potential therapeutic interventions. Science , this issue p. eabc8511 , p. 1210 more...
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- 2020
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9. SARS-CoV-2 Seroprevalence Among Parturient Women
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Claudia P. Arevalo, Jeanette Dougherty, Allison R. Greenplate, Daniel J. Rader, Eileen C. Goodwin, Divij Mathew, Laura A. Vella, Nicholas Han, Marcus J. Bolton, Olivia Kuthuru, Ajinkya Pattekar, Emily C. Woodford, Anurag Verma, Scott E. Hensley, Miren B. Dhudasia, Dustin D. Flannery, Justin Kim, Jeffrey S. Morris, Madison E. Weirick, E. John Wherry, Karen M. Puopolo, Amy E. Baxter, Sagori Mukhopadhyay, JoEllen Weaver, Rita Leite, Michal A. Elovitz, Madeline R. Pfeifer, Elizabeth M. Anderson, Jeffrey S. Gerber, and Sigrid Gouma more...
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medicine.medical_specialty ,Pregnancy ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Obstetrics ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,medicine ,Seroprevalence ,medicine.disease ,business ,Serology - Abstract
Limited data are available for pregnant women affected by SARS-CoV-2. Serological tests are critically important to determine exposure and immunity to SARS-CoV-2 within both individuals and populations. We completed SARS-CoV-2 serological testing of 1,293 parturient women at two centers in Philadelphia from April 4 to June 3, 2020. We tested 834 pre-pandemic samples collected in 2019 and 15 samples from COVID-19 recovered donors to validate our assay, which has a ∼1% false positive rate. We found 80/1,293 (6.2%) of parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies. We found race/ethnicity differences in seroprevalence rates, with higher rates in Black/non-Hispanic and Hispanic/Latino women. Of the 72 seropositive women who also received nasopharyngeal polymerase chain reaction testing during pregnancy, 46 (64%) were positive. Continued serologic surveillance among pregnant women may inform perinatal clinical practices and can potentially be used to estimate seroprevalence within the community.One Sentence SummarySix percent of pregnant women delivering from April 4 to June 3, 2020 had serological evidence of exposure to SARS-CoV-2 with notable race/ethnicity differences in seroprevalence rates. more...
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- 2020
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10. SARS-CoV-2 seroprevalence among parturient women in Philadelphia
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Emily C. Woodford, Scott E. Hensley, Rita Leite, Divij Mathew, Sigrid Gouma, Justin Kim, Marcus J. Bolton, Ajinkya Pattekar, Anurag Verma, Miren B. Dhudasia, Michal A. Elovitz, Madison E. Weirick, Dustin D. Flannery, JoEllen Weaver, Nicholas Han, Amy E. Baxter, Claudia P. Arevalo, Jeanette Dougherty, Madeline R. Pfeifer, Daniel J. Rader, Eileen C. Goodwin, Allison R. Greenplate, Elizabeth M. Anderson, Jeffrey S. Morris, E. John Wherry, Karen M. Puopolo, Laura A. Vella, Sagori Mukhopadhyay, Oliva Kuthuru, and Jeffrey S. Gerber more...
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0301 basic medicine ,Antibodies, Viral ,Serology ,Cohort Studies ,COVID-19 Testing ,0302 clinical medicine ,Pregnancy ,Seroepidemiologic Studies ,Pandemic ,Medicine ,Pregnancy Complications, Infectious ,Young adult ,Philadelphia ,030219 obstetrics & reproductive medicine ,biology ,Obstetrics ,Hispanic or Latino ,General Medicine ,Spike Glycoprotein, Coronavirus ,Female ,Antibody ,Coronavirus Infections ,Cohort study ,Adult ,medicine.medical_specialty ,Pneumonia, Viral ,Immunology ,Article ,Betacoronavirus ,Young Adult ,03 medical and health sciences ,Protein Domains ,Humans ,Seroprevalence ,Pandemics ,Clinical Laboratory Techniques ,SARS-CoV-2 ,business.industry ,fungi ,COVID-19 ,Health Status Disparities ,medicine.disease ,Black or African American ,Coronavirus ,030104 developmental biology ,Immunoglobulin M ,Immunoglobulin G ,biology.protein ,business ,Reports - Abstract
Limited data are available for pregnant women affected by SARS-CoV-2. Serological tests are critically important to determine exposure and immunity to SARS-CoV-2 within both individuals and populations. We completed SARS-CoV-2 serological testing of 1,293 parturient women at two centers in Philadelphia from April 4 to June 3, 2020. We tested 834 pre-pandemic samples collected in 2019 and 15 samples from COVID-19 recovered donors to validate our assay, which has a ~1% false positive rate. We found 80/1,293 (6.2%) of parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies. We found race/ethnicity differences in seroprevalence rates, with higher rates in Black/non-Hispanic and Hispanic/Latino women. Of the 72 seropositive women who also received nasopharyngeal polymerase chain reaction testing during pregnancy, 46 (64%) were positive. Continued serologic surveillance among pregnant women may inform perinatal clinical practices and can potentially be used to estimate seroprevalence within the community., One Sentence Summary: Six percent of pregnant women delivering from April 4 to June 3, 2020 had serological evidence of exposure to SARS-CoV-2 with notable race/ethnicity differences in seroprevalence rates. more...
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- 2020
11. Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection
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Leticia Kuri-Cervantes, M. Betina Pampena, Wenzhao Meng, Aaron M. Rosenfeld, Caroline A.G. Ittner, Ariel R. Weisman, Roseline Agyekum, Divij Mathew, Amy E. Baxter, Laura Vella, Oliva Kuthuru, Sokratis Apostolidis, Luanne Bershaw, Jeannete Dougherty, Allison R. Greenplate, Ajinkya Pattekar, Justin Kim, Nicholas Han, Sigrid Gouma, Madison E. Weirick, Claudia P. Arevalo, Marcus J. Bolton, Eileen C. Goodwin, Elizabeth M. Anderson, Scott E. Hensley, Tiffanie K. Jones, Nilam S. Mangalmurti, Eline T. Luning Prak, E. John Wherry, Nuala J. Meyer, and Michael R. Betts more...
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Coronavirus disease 2019 (COVID-19) ,biology ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,macromolecular substances ,biochemical phenomena, metabolism, and nutrition ,Phenotype ,Peripheral blood ,Article ,medicine.anatomical_structure ,Immune system ,Critical illness ,Immunology ,biology.protein ,medicine ,Antibody ,B cell - Abstract
Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified broad changes in neutrophils, NK cells, and monocytes during severe COVID-19, suggesting excessive mobilization of innate lineages. We found marked activation within T and B cells, highly oligoclonal B cell populations, profound plasmablast expansion, and SARS-CoV-2-specific antibodies in many, but not all, severe COVID-19 cases. Despite this heterogeneity, we found selective clustering of severe COVID-19 cases through unbiased analysis of the aggregated immunological phenotypes. Our findings demonstrate broad immune perturbations spanning both innate and adaptive leukocytes that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.One Sentence SummaryBroad immune perturbations in severe COVID-19 more...
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- 2020
12. The feasibility and acceptability of collecting psychosocial outcome measures embedded within a precision medicine trial for childhood cancer
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Eden G. Robertson, Kate Hetherington, Rebecca Daly, Mark W. Donoghoe, Nicholas Handelsman, David S. Ziegler, and Claire E. Wakefield
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acceptability ,clinical trial ,feasibility ,oncology ,outcome measures ,paediatric ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Patient‐reported outcomes measures (PROMs) are increasingly being collected within cancer clinical trials, yet limited literature on the feasibility and acceptability of doing so. Methods We collected parent‐proxy and adolescent (≥12 years old) PROMs through a longitudinal, psychosocial sub‐study (‘PRISM‐Impact’) embedded in a precision medicine trial for children with poor prognosis cancer (‘PRISM’). We report on feasibility (response, participation, and attrition rates; follow‐up and responding to elevated distress) and acceptability (parents’ perceived benefit/burden of participation; and impact on decision to participate in PRISM) of PRISM‐Impact. Results Over the reporting period, 462 families were eligible for PRISM‐Impact. Family and adolescent response rates were 53% and 45%, respectively. Parents whose child had relapsed were more likely to participate in PRISM‐Impact than parents whose child had not (p more...
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- 2024
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13. Ion Transport in Cyclopropenium-Based Polymerized Ionic Liquids
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Xiaodong Yin, Karen I. Winey, Nicholas Han, Jessica L. Freyer, Tristan H. Lambert, Philip J. Griffin, Luis M. Campos, Chirag D. Gheewala, and Noah Geller
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chemistry.chemical_classification ,Materials science ,Polymers and Plastics ,Organic Chemistry ,Ionic bonding ,02 engineering and technology ,Polymer ,Conductivity ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,Ion ,Inorganic Chemistry ,chemistry.chemical_compound ,chemistry ,Chemical physics ,Ionic liquid ,Materials Chemistry ,Ionic conductivity ,Counterion ,0210 nano-technology ,Ion transporter - Abstract
Ion transport in polymerized ionic liquids (poly-ILs) occurs via a fundamentally different mechanism than in monomeric ionic liquids, and recently progress has been made toward understanding ion conduction in poly-ILs. To gain insight into the nature of ionic conductivity in ionic polymers, we investigate the physical properties of the trisaminocyclopropenium (TAC) ion, as it is an aromatic carbocation with unique structural and electronic properties. Herein, we characterize the thermal properties, local morphology, and dielectric response of a series of monomeric and polymeric TAC ionic liquids with different counterions. We have found that the extent of a “superionic” mechanism depends on the nature of the ion pair and can result in anomalously high conductivity at the calorimetric Tg. Our results suggest that the molecular volumes of the cationic and anionic species are important parameters that impact ion conductivity in polymerized ionic liquids. more...
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- 2018
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14. Impact of Water Ionic Chemistry on Kombucha Fermentation
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Katherine A. Thompson-Witrick, Olivia Sundman, Sadie Disselkoen, Nicholas Hanson, Cheyenne Butler, Victoria Jordan, Ian Galbraith, Jada Spake, Seiler Pollock, and Drew M. Budner
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kombucha ,fermentation ,antioxidant ,water ,chemical composition ,Nutrition. Foods and food supply ,TX341-641 ,Nutritional diseases. Deficiency diseases ,RC620-627 - Abstract
Kombucha is made by using a symbiotic culture of bacteria and yeast (SCOBY) to ferment sweetened tea. This fermentation produces a beverage with a unique aroma and acidic flavor. Kombucha has recently gained popularity in the United States and has been reported to have numerous health benefits. While there is a wide variation in kombucha composition, little is known about the impact water’s chemistry has on the fermentation and the resulting kombucha. Brewing water for kombucha was altered using the following ions: bicarbonate, chloride, calcium, magnesium, and sulfate at different concentrations. Pre-(tea) and post-(kombucha) fermentation (kombucha) products were analyzed for total acidity, pH, free amino nitrogen (FAN), total phenols, antioxidants, and biological components. A one-way ANOVA was run to determine statistical (p < 0.05) differences between the characteristics analyzed. Statistical differences were observed between the different water chemistry ions for all of the characteristics analyzed. Further investigation into the impact water chemistry has on flavor analysis is required. The information obtained from this research can be used to help producers to make kombuchas with an optimized chemical profile and improved antioxidant potentials. more...
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- 2024
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15. Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection
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Anurag Verma, Jeanette Dougherty, Paul Bates, Leticia Kuri-Cervantes, Eileen C. Goodwin, Michael R. Betts, Laura A. Vella, Shannon R. Christensen, Madison E. Weirick, Oliva Kuthuru, Nicholas Han, Divij Mathew, Tomaz B. Manzoni, E. John Wherry, Christopher M McAllister, M. Betina Pampena, Jennifer E. Wu, Holly Ramage, Derek A. Oldridge, Elizabeth M. Anderson, Nuala J. Meyer, Allison R. Greenplate, Kurt D'Andrea, Claudia P. Arevalo, Alexander C. Huang, Philip Hicks, Oluwatosin Oniyide, Cécile Alanio, Sara Cherry, Sigrid Gouma, Scott E. Hensley, Ajinkya Pattekar, Justin Kim, JoEllen Weaver, Amy E. Baxter, Marcus J. Bolton, Daniel J. Rader, and Sokratis A. Apostolidis more...
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Cross Protection ,viruses ,coronavirus ,Antibodies, Viral ,medicine.disease_cause ,Alphacoronavirus ,0302 clinical medicine ,antibody ,Chlorocebus aethiops ,Pandemic ,Child ,skin and connective tissue diseases ,Coronavirus ,0303 health sciences ,education.field_of_study ,virus diseases ,Human coronavirus ,Child, Preschool ,Cohort ,Disease Susceptibility ,Antibody ,Adult ,Adolescent ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Population ,Cross Reactions ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,COVID-19 Serological Testing ,Betacoronavirus ,03 medical and health sciences ,medicine ,Animals ,Humans ,education ,Vero Cells ,030304 developmental biology ,SARS-CoV-2 ,fungi ,Infant, Newborn ,COVID-19 ,Infant ,Serum samples ,biology.organism_classification ,Virology ,body regions ,HEK293 Cells ,Vero cell ,biology.protein ,030217 neurology & neurosurgery - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread within the human population. Although SARS-CoV-2 is a novel coronavirus, most humans had been previously exposed to other antigenically distinct common seasonal human coronaviruses (hCoVs) before the COVID-19 pandemic. Here, we quantified levels of SARS-CoV-2-reactive antibodies and hCoV-reactive antibodies in serum samples collected from 431 humans before the COVID-19 pandemic. We then quantified pre-pandemic antibody levels in serum from a separate cohort of 251 individuals who became PCR-confirmed infected with SARS-CoV-2. Finally, we longitudinally measured hCoV and SARS-CoV-2 antibodies in the serum of hospitalized COVID-19 patients. Our studies indicate that most individuals possessed hCoV-reactive antibodies before the COVID-19 pandemic. We determined that ∼20% of these individuals possessed non-neutralizing antibodies that cross-reacted with SARS-CoV-2 spike and nucleocapsid proteins. These antibodies were not associated with protection against SARS-CoV-2 infections or hospitalizations, but they were boosted upon SARS-CoV-2 infection., Analysis of human serum samples before and after the onset of the COVID-19 pandemic show that antibodies against common seasonal human coronaviruses are cross-reactive against SARS-CoV-2 but do not confer cross-protection against infection or hospitalization. more...
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- 2021
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16. Axon morphology and intrinsic cellular properties determine repetitive transcranial magnetic stimulation threshold for plasticity
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Christos Galanis, Lena Neuhaus, Nicholas Hananeia, Zsolt Turi, Peter Jedlicka, and Andreas Vlachos
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synaptic plasticity ,morphology ,axons ,inhibition ,excitation ,whole-cell patch-clamp recordings ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
IntroductionRepetitive transcranial magnetic stimulation (rTMS) is a widely used therapeutic tool in neurology and psychiatry, but its cellular and molecular mechanisms are not fully understood. Standardizing stimulus parameters, specifically electric field strength, is crucial in experimental and clinical settings. It enables meaningful comparisons across studies and facilitates the translation of findings into clinical practice. However, the impact of biophysical properties inherent to the stimulated neurons and networks on the outcome of rTMS protocols remains not well understood. Consequently, achieving standardization of biological effects across different brain regions and subjects poses a significant challenge.MethodsThis study compared the effects of 10 Hz repetitive magnetic stimulation (rMS) in entorhino-hippocampal tissue cultures from mice and rats, providing insights into the impact of the same stimulation protocol on similar neuronal networks under standardized conditions.ResultsWe observed the previously described plastic changes in excitatory and inhibitory synaptic strength of CA1 pyramidal neurons in both mouse and rat tissue cultures, but a higher stimulation intensity was required for the induction of rMS-induced synaptic plasticity in rat tissue cultures. Through systematic comparison of neuronal structural and functional properties and computational modeling, we found that morphological parameters of CA1 pyramidal neurons alone are insufficient to explain the observed differences between the groups. Although morphologies of mouse and rat CA1 neurons showed no significant differences, simulations confirmed that axon morphologies significantly influence individual cell activation thresholds. Notably, differences in intrinsic cellular properties were sufficient to account for the 10% higher intensity required for the induction of synaptic plasticity in the rat tissue cultures.ConclusionThese findings demonstrate the critical importance of axon morphology and intrinsic cellular properties in predicting the plasticity effects of rTMS, carrying valuable implications for the development of computer models aimed at predicting and standardizing the biological effects of rTMS. more...
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- 2024
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17. Outpatient albumin infusions reduce hospitalizations and improve outcomes in decompensated cirrhosis: A real‐world cohort study
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Nicholas Hannah, Douglas Tjandra, Ashwin Patwardhan, Kelsey Rutland, John Halliday, and Siddharth Sood
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albumin ,ascites ,cirrhosis ,hospitalization ,outpatient ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background and Aim Long‐term human albumin (HA) infusions improve survival in cirrhotic patients with diuretic resistant ascites. We aimed to determine whether there is a significant benefit in a more unwell real‐world cohort. Methods This is a single‐center retrospective cohort study. Patients received outpatient HA between April 2017 and June 2021. Inclusion criteria were age ≥18 years, cirrhosis with ascites, and received at least 1 month of HA. Patients with significant comorbidities and ongoing alcohol use were not excluded. Outcomes assessed were transjugular intrahepatic portosystemic shunt (TIPS)/transplant‐free survival (TTFS), and biochemical and prognostic outcomes. Results Twenty‐four patients were included. Median age was 59.5 years. Seven were female (29.2%). Etiology included were alcohol (50%), non‐alcoholic steatohepatitis (16.7%), and viral/alcohol (12.5%). Median model for end‐stage liver disease‐sodium (MELD‐Na) was 18.5, with Child–Pugh scores (CPS) A (4.2%), B (50%), and C (45.8%). Improvements in serum sodium (P = 0.014), albumin (P = 0.003), and CPS (P = 0.017) were observed. Reduction in hospitalizations (P = 0.001), particularly portal hypertensive related admissions was observed (relative risk 0.39; 95% confidence interval [CI] 0.21–0.69, P = 0.003), needed to treat 2.09 (95% CI 1.25–3.67). There was a reduction in total paracentesis requirements (P = 0.005). On multivariate analysis, type 2 diabetes mellitus significantly increased risk of TIPS/transplant/death (hazard ratio 6.16; 95% CI 1.23–30.84, P = 0.027). Median TTFS improved in patients with a change in MELD‐Na ≤1 at 1 month: 29.4 months versus 7.7 months (P = 0.011). Conclusion Outpatient HA infusions decrease portal hypertensive related hospital admissions, improve serum sodium, albumin levels, and CPS. Type 2 diabetes mellitus and change in MELD‐Na score help discriminate those likely to benefit most. more...
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- 2023
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18. Effectiveness and Tolerability of Anti-Calcitonin Gene-Related Peptide Therapy for Migraine and Other Chronic Headaches in Adolescents and Young Adults: A Retrospective Study in the USA
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Anjaneya Shankar Madhav Bandatmakur, Pooja Dave, Melissa Kerr, Colin Brunick, Sijin Wen, and Nicholas Hansen
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pediatric headache ,migraine ,anti-CGRP ,headache ,anti-migraine treatment ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
This retrospective study assesses the efficacy and tolerability of anti-calcitonin gene-related peptide (anti-CGRP) therapy in adolescents and young adults (ages 12–21) with migraine and chronic daily headaches unresponsive to standard treatments. Migraines in this demographic significantly impair school performance, self-esteem, psychological well-being, and cognitive health. These young patients are also particularly sensitive to the side effects of conventional medications, which are often prescribed off-label and come with high insurance denial rates. Medication overuse, including analgesics, triptans, and NSAIDs, is prevalent due to treatment failures. Elevated plasma CGRP levels observed during migraines suggest that anti-CGRP therapies, successful in adult populations, may also benefit this younger age group. Over a three-year period, patients at a specialized pediatric headache center were evaluated for the impact of anti-CGRP treatments, including monoclonal antibodies (erenumab, fremanezumab, and galcanezumab) and small-molecule CGRP receptor antagonists (ubrogepant, rimegepant, and atogepant), administered either alone or in combination with OnabotulinumtoxinA. Data were extracted from the hospital’s electronic medical records, and patient progress was consistently documented using a structured template for each clinic visit. Additional patient satisfaction data were collected via telephone follow-ups and patient message reviews. The study included 23 patients, primarily treated for chronic migraine (CM) (78.3%), with a smaller subset addressing episodic migraine (EM), new daily persistent headaches (NDPHs), and post-traumatic headaches (PTHs). Comprehensive demographic and clinical data, including age, treatment duration, history of preventive treatment failures, and comorbidities like psychiatric conditions and sleep disorders, were collected. Anti-CGRP therapies, particularly when combined with traditional treatments or OnabotulinumtoxinA, resulted in significant improvements: 91.3% of patients experienced reduced migraine duration and intensity, 82.6% reported improvements in other bothersome symptoms, and 73.9% saw an improved response to rescue medications. Additionally, 78.3% of patients reported a reduction in their use of rescue medications per week by more than 50%, and emergency room visits were reduced for 56.5% of patients. Significant reductions in headache days were observed in 82.6% of patients after one month and 87% after three months, with nearly 40% experiencing more than a 50% reduction in both periods. The greatest benefits were observed in patients treated for more than six months. Adverse effects were minimal, with 95.7% of patients reporting no side effects, and patient satisfaction was high, with 69.6% opting to continue treatment. Overall, this study highlights the substantial potential of anti-CGRP therapy in improving outcomes for adolescents and young adults with CM and EM, offering a promising approach for a demographic that faces considerable challenges with conventional treatment options. However, further research is needed to confirm these findings and expand clinical applications in this age group. more...
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- 2024
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19. Increased iron in the substantia nigra pars compacta identifies patients with early Parkinson’s disease: A 3T and 7T MRI study
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Erind Alushaj, Nicholas Handfield-Jones, Alan Kuurstra, Anisa Morava, Ravi S. Menon, Adrian M. Owen, Manas Sharma, Ali R. Khan, and Penny A. MacDonald
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Parkinson’s disease ,Neuroimaging ,Quantitative susceptibility mapping ,Iron ,Midbrain ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Degeneration in the substantia nigra (SN) pars compacta (SNc) underlies motor symptoms in Parkinson’s disease (PD). Currently, there are no neuroimaging biomarkers that are sufficiently sensitive, specific, reproducible, and accessible for routine diagnosis or staging of PD. Although iron is essential for cellular processes, it also mediates neurodegeneration. MRI can localize and quantify brain iron using magnetic susceptibility, which could potentially provide biomarkers of PD.We measured iron in the SNc, SN pars reticulata (SNr), total SN, and ventral tegmental area (VTA), using quantitative susceptibility mapping (QSM) and R2* relaxometry, in PD patients and age-matched healthy controls (HCs). PD patients, diagnosed within five years of participation and HCs were scanned at 3T (22 PD and 23 HCs) and 7T (17 PD and 21 HCs) MRI. Midbrain nuclei were segmented using a probabilistic subcortical atlas. QSM and R2* values were measured in midbrain subregions. For each measure, groups were contrasted, with Age and Sex as covariates, and receiver operating characteristic (ROC) curve analyses were performed with repeated k-fold cross-validation to test the potential of our measures to classify PD patients and HCs. Statistical differences of area under the curves (AUCs) were compared using the Hanley-MacNeil method (QSM versus R2*; 3T versus 7T MRI).PD patients had higher QSM values in the SNc at both 3T (padj = 0.001) and 7T (padj = 0.01), but not in SNr, total SN, or VTA, at either field strength. No significant group differences were revealed using R2* in any midbrain region at 3T, though increased R2* values in SNc at 7T MRI were marginally significant in PDs compared to HCs (padj = 0.052). ROC curve analyses showed that SNc iron measured with QSM, distinguished early PD patients from HCs at the single-subject level with good diagnostic accuracy, using 3T (mean AUC = 0.83, 95 % CI = 0.82–0.84) and 7T (mean AUC = 0.80, 95 % CI = 0.79–0.81) MRI. Mean AUCs reported here are from averages of tests in the hold-out fold of cross-validated samples. The Hanley-MacNeil method demonstrated that QSM outperforms R2* in discriminating PD patients from HCs at 3T, but not 7T. There were no significant differences between 3T and 7T in diagnostic accuracy of QSM values in SNc.This study highlights the importance of segmenting midbrain subregions, performed here using a standardized atlas, and demonstrates high accuracy of SNc iron measured with QSM at 3T MRI in identifying early PD patients. QSM measures of SNc show potential for inclusion in neuroimaging diagnostic biomarkers of early PD. An MRI diagnostic biomarker of PD would represent a significant clinical advance. more...
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- 2024
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20. Indoor Infrastructure Maintenance Framework Using Networked Sensors, Robots, and Augmented Reality Human Interface
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Alireza Fath, Nicholas Hanna, Yi Liu, Scott Tanch, Tian Xia, and Dryver Huston
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Home Maintenance 4.0 ,human–building interaction ,quadruped robot dog ,microrobot ,augmented reality ,machine learning ,Information technology ,T58.5-58.64 - Abstract
Sensing and cognition by homeowners and technicians for home maintenance are prime examples of human–building interaction. Damage, decay, and pest infestation present signals that humans interpret and then act upon to remedy and mitigate. The maintenance cognition process has direct effects on sustainability and economic vitality, as well as the health and well-being of building occupants. While home maintenance practices date back to antiquity, they readily submit to augmentation and improvement with modern technologies. This paper describes the use of networked smart technologies embedded with machine learning (ML) and presented in electronic formats to better inform homeowners and occupants about safety and maintenance issues, as well as recommend courses of remedial action. The demonstrated technologies include robotic sensing in confined areas, LiDAR scans of structural shape and deformation, moisture and gas sensing, water leak detection, network embedded ML, and augmented reality interfaces with multi-user teaming capabilities. The sensor information passes through a private local dynamic network to processors with neural network pattern recognition capabilities to abstract the information, which then feeds to humans through augmented reality and conventional smart device interfaces. This networked sensor system serves as a testbed and demonstrator for home maintenance technologies, for what can be termed Home Maintenance 4.0. more...
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- 2024
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21. Resilience, depression and their effect on nurse retention: a survey in rural Indonesia
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Ika Buntoro, Conrad Folamauk, Rr Listyawati Nurina, Simon Kleden, and Nicholas Handoyo
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Special situations and conditions ,RC952-1245 ,Public aspects of medicine ,RA1-1270 - Abstract
Introduction: Health professionals' maldistribution and retention in underserved areas are global problems. Burnout drives health professionals to leave rural areas. Chronic burnout is linked to depression, and nurses have a higher risk for depression than the general population. Studies suggest that increasing resilience may reduce depression. However, little is known about the effect of resilience on nurses' depression and their rural retention. This study aims to understand the impact of resilience and depression on nurses' retention in rural areas.Methods: An online cross-sectional survey on registered nurses was conducted in July - August 2021 in a rural province in Indonesia. The survey measured the nurses' resilience, depression level, and work duration.Results: A total of 1050 participants joined the study. The results suggest that resilience in nurses is negatively correlated to depression and retention. The mildly depressed group had the shortest retention. There was no difference in the work duration, depression, and resilience scores between the underserved and non-underserved regencies in the province.Discussion: Although not all our hypotheses are supported, some interesting results were obtained. In a previous study, the more senior the doctor, the higher the resilience; in this nurse analysis, the opposite was true - senior nurses were the least resilient. As found in other studies, resilience is negatively correlated to depression. So, resilience training may still benefit the depressed group.Conclusion: Improvement of health professionals' rural retention requires approaches tailored to each profession. Resilience training may be beneficial to retain nurses through mild depression treatment. Keywords: depression, nurse, resilience, rural retention, Indonesia. more...
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- 2023
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22. Multi-scale modeling toolbox for single neuron and subcellular activity under Transcranial Magnetic Stimulation
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Sina Shirinpour, Nicholas Hananeia, James Rosado, Harry Tran, Christos Galanis, Andreas Vlachos, Peter Jedlicka, Gillian Queisser, and Alexander Opitz
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Transcranial magnetic stimulation ,Electric field simulation ,Neuron compartmental modeling ,Calcium simulation ,Three-dimensional reconstructions ,Synaptic plasticity ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Background: Transcranial Magnetic Stimulation (TMS) is a widely used non-invasive brain stimulation method. However, its mechanism of action and the neural response to TMS are still poorly understood. Multi-scale modeling can complement experimental research to study the subcellular neural effects of TMS. At the macroscopic level, sophisticated numerical models exist to estimate the induced electric fields. However, multi-scale computational modeling approaches to predict TMS cellular and subcellular responses, crucial to understanding TMS plasticity inducing protocols, are not available so far. Objective: We develop an open-source multi-scale toolbox Neuron Modeling for TMS (NeMo-TMS) to address this problem. Methods: NeMo-TMS generates accurate neuron models from morphological reconstructions, couples them to the external electric fields induced by TMS, and simulates the cellular and subcellular responses of single-pulse and repetitive TMS. Results: We provide examples showing some of the capabilities of the toolbox. Conclusion: NeMo-TMS toolbox allows researchers a previously not available level of detail and precision in realistically modeling the physical and physiological effects of TMS. more...
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- 2021
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23. Dosing Transcranial Magnetic Stimulation of the Primary Motor and Dorsolateral Prefrontal Cortices With Multi-Scale Modeling
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Zsolt Turi, Nicholas Hananeia, Sina Shirinpour, Alexander Opitz, Peter Jedlicka, and Andreas Vlachos
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transcranial magnetic stimulation ,repetitive transcranial magnetic stimulation ,electric field ,multi-scale modeling ,primary motor cortex ,dorsolateral prefrontal cortex ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Transcranial magnetic stimulation (TMS) can depolarize cortical neurons through the intact skin and skull. The characteristics of the induced electric field (E-field) have a major impact on specific outcomes of TMS. Using multi-scale computational modeling, we explored whether the stimulation parameters derived from the primary motor cortex (M1) induce comparable macroscopic E-field strengths and subcellular/cellular responses in the dorsolateral prefrontal cortex (DLPFC). To this aim, we calculated the TMS-induced E-field in 16 anatomically realistic head models and simulated the changes in membrane voltage and intracellular calcium levels of morphologically and biophysically realistic human pyramidal cells in the M1 and DLPFC. We found that the conventional intensity selection methods (i.e., motor threshold and fixed intensities) produce variable macroscopic E-fields. Consequently, it was challenging to produce comparable subcellular/cellular responses across cortical regions with distinct folding characteristics. Prospectively, personalized stimulation intensity selection could standardize the E-fields and the subcellular/cellular responses to repetitive TMS across cortical regions and individuals. The suggested computational approach points to the shortcomings of the conventional intensity selection methods used in clinical settings. We propose that multi-scale modeling has the potential to overcome some of these limitations and broaden our understanding of the neuronal mechanisms for TMS. more...
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- 2022
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24. Toward a Simulation Model Complexity Measure
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J. Scott Thompson, Douglas D. Hodson, Michael R. Grimaila, Nicholas Hanlon, and Richard Dill
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simulation model ,complexity ,Kolmogorov complexity ,normalized compression distance ,resolution ,scope ,Information technology ,T58.5-58.64 - Abstract
Is it possible to develop a meaningful measure for the complexity of a simulation model? Algorithmic information theory provides concepts that have been applied in other areas of research for the practical measurement of object complexity. This article offers an overview of the complexity from a variety of perspectives and provides a body of knowledge with respect to the complexity of simulation models. The key terms model detail, resolution, and scope are defined. An important concept from algorithmic information theory, Kolmogorov complexity, and an application of this concept, normalized compression distance, are used to indicate the possibility of measuring changes in model detail. Additional research in this area can advance the modeling and simulation body of knowledge toward the practical application of measuring simulation model complexity. Examples show that KC and NCD measurements of simulation models can detect changes in scope and detail. more...
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- 2023
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25. Open-source toolbox for multi-scale modeling of single neurons under transcranial magnetic stimulation
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Sina Shirinpour, Nicholas Hananeia, James Rosado, Harry Tran, Christos Galanis, Andreas Vlachos, Peter Jedlicka, Gillian Queisser, and Alexander Opitz
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Published
- 2021
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26. Personal resilience and rural doctors retention: a study in Indonesia
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Nicholas Handoyo, Gandes Rahayu, Mora Claramita, Julie Ash, and Lambert Schuwirth
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general practitioner ,Indonesia ,personal resilience ,rural retention. ,Special situations and conditions ,RC952-1245 ,Public aspects of medicine ,RA1-1270 - Abstract
Introduction: Retaining the health workforce in rural areas is a global problem. Job dissatisfaction or work-related distress are among the factors that drive doctors to leave rural places. Resilience has been recognised as a key component of wellbeing and is associated with better satisfaction with life. Building personal resilience has the benefits of lowering vulnerability to work-related adversity. This study examined the association between rural doctors' personal resilience and the duration of rural practice. Methods: This cross-sectional study was set in a rural province in Indonesia. A total sampling procedure was implemented. A total of 528 participants responded to an online survey. The survey tool measured six dimensions of a resilience profile (determination, endurance, adaptability, recuperability, comfort zone and life calling) and collected personal data such as date of birth, practice location and duration of rural practice experience. These participants were classified into four groups: intern, general (GP) with 10 years experience. The data were analysed quantitatively using Oneway analysis of variance (ANOVA). Results: Doctors with longer durations of rural experience showed higher resilience levels in four of the dimensions of personal resilience: endurance, adaptability, recuperability and comfort zone. Among those four dimensions, endurance and comfort zone showed significant differences between groups with >10 years of difference in rural experience (p more...
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- 2020
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27. Complex housing causes a robust increase in dendritic complexity and spine density of medial prefrontal cortical neurons
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Archana Ashokan, Jamien Wee Han Lim, Nicholas Hang, and Rupshi Mitra
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Medicine ,Science - Abstract
Abstract Prelimbic cortex and infralimbic cortex, parts of the ventromedial prefrontal cortex, are critical brain regions for generating a flexible behavioral response to changing environmental contingencies. This includes the role of these brain structures in the extinction of learned fear, decision making and retrieval of remote memories. Dendritic structure of medial prefrontal cortex neurons retains significant structural plasticity in adulthood. This has been mainly demonstrated as dendritic atrophy and loss of dendritic spines due to chronic stress. It remains unknown if housing condition of the animals itself can cause opposing changes in the dendritic organization. In that backdrop, here we report that short-term increase in complexity of the housing causes a robust increase in complexity of dendritic architecture of prelimbic and infralimbic neurons. This is reflected in the dendritic expansion of prelimbic neurons and increase in spine density of prelimbic and infralimbic neurons. These results suggest that non-invasive changes in the housing environment can be harnessed to study brain reserves for the flexible and species-typical behaviors. more...
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- 2018
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28. The Many Faces of Innate Immunity in SARS-CoV-2 Infection
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Nicholas Hanan, Ronnie L. Doud, In-Woo Park, Harlan P. Jones, and Stephen O. Mathew
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SARS-CoV-2 ,COVID-19 ,innate immunity ,cytokines ,Medicine - Abstract
The innate immune system is important for initial antiviral response. SARS-CoV-2 can result in overactivity or suppression of the innate immune system. A dysregulated immune response is associated with poor outcomes; with patients having significant Neutrophil-to-Lymphocyte ratios (NLR) due to neutrophilia alongside lymphopenia. Elevated interleukin (IL)-6 and IL-8 leads to overactivity and is a prominent feature of severe COVID-19 patients. IL-6 can result in lymphopenia; where COVID-19 patients typically have significantly altered lymphocyte subsets. IL-8 attracts neutrophils; which may play a significant role in lung tissue damage with the formation of neutrophil extracellular traps leading to cytokine storm or acute respiratory distress syndrome. Several factors like pre-existing co-morbidities, genetic risks, viral pathogenicity, and therapeutic efficacy act as important modifiers of SARS-CoV-2 risks for disease through an interplay with innate host inflammatory responses. In this review, we discuss the role of the innate immune system at play with other important modifiers in SARS-CoV-2 infection. more...
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- 2021
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29. The Challenge of Implementing the Marine Ecosystem Service Concept
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Michael Townsend, Kate Davies, Nicholas Hanley, Judi E. Hewitt, Carolyn J. Lundquist, and Andrew M. Lohrer
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connectivity ,data scarcity ,ecosystem services ,mapping ,marine ,measuring ,Science ,General. Including nature conservation, geographical distribution ,QH1-199.5 - Abstract
The concept of ecosystem services has gained traction as a means of linking societal benefits to the underlying ecology and functioning of ecosystems, and is now frequently included in decision-making and legislation. Moving the ecosystem service concept from theory into practice is now crucial. However, advancements in this area of research differ by ecosystem type, and marine systems lag significantly behind terrestrial counterparts in terms of understanding, implementation, and number of studies. In this paper we explore several reasons why ecosystem service research has been limited in marine systems and we outline the challenges that hinder progress. Marine systems suffer from a scarcity of spatial data relative to terrestrial counterparts. In terrestrial systems the spatial patterns of land-use/land-cover (LULC) are relatively straightforward to access via satellite and have been used as proxy indicators of service provisions. In contrast, remote sensing tools used to study the surface of the Earth are much less effective at capturing images of the seabed, and by extension marine habitats. Marine waters and their constituents are also frequently driven great distances by winds, tides, and currents. This creates a challenge for management as the identification and protection of areas where ecosystem services are exploited is not necessarily sufficient to ensure sustained service delivery. Further complications arise from the three-dimensional uses of marine systems, incorporating activities that use the sea surface, the water column and the benthic habitats below. Progress is being made as technological advancements are resulting in the acquisition of spatial data at faster rates and higher resolutions than previously possible. There is a growing capacity to map, model and value an increasing number of services with initiatives such as InVEST or principle-based modeling. We suggest that awareness is needed around the limited progress in marine systems as this could affect the way we value the biosphere and the relative proportion between biomes. more...
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- 2018
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30. Vertical organization of the division of labor within nests of the Florida harvester ant, Pogonomyrmex badius.
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Walter R Tschinkel and Nicholas Hanley
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Medicine ,Science - Abstract
In the Florida harvester ant, Pogonomyrmex badius, foragers occur only in the top 15 cm of the nest, whereas brood and brood-care workers reside mostly in the deepest regions, yet the food and seeds foragers collect must be transported downward 30 to 80 cm to seed chambers and up to 2 m to brood chambers. Using mark-recapture techniques with fluorescent printer's ink, we identified a class of workers that ranges widely within the vertical structure of the nest, rapidly moving materials dropped by foragers in the upper regions downward, and excavated soil from deeper upward. Within the nest, only 5% of foragers were recovered below 20 cm depth, but about 30% of transfer workers and 82% of unmarked workers were found there. Below 70 cm depth, 90% of workers were unmarked, and were probably involved mostly in brood care. During the summer, the transfer workers comprise about a quarter of the nest population, while foragers make up about 40%. Workers marked as transfer workers later appear as foragers, while those marked as foragers die and disappear from the foraging population, suggesting that transfer workers are younger, and age into foraging. The importance of these findings for laboratory studies of division of labor are discussed. The efficient allocation of labor is a key component of superorganismal fitness. more...
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- 2017
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31. Drivers of Public Attitudes towards Small Wind Turbines in the UK.
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Cerian Tatchley, Heather Paton, Emma Robertson, Jeroen Minderman, Nicholas Hanley, and Kirsty Park
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Medicine ,Science - Abstract
Small Wind Turbines (SWTs) are a growing micro-generation industry with over 870,000 installed units worldwide. No research has focussed on public attitudes towards SWTs, despite evidence the perception of such attitudes are key to planning outcomes and can be a barrier to installations. Here we present the results of a UK wide mail survey investigating public attitudes towards SWTs. Just over half of our respondents, who were predominantly older, white males, felt that SWTs were acceptable across a range of settings, with those on road signs being most accepted and least accepted in hedgerows and gardens. Concern about climate change positively influenced how respondents felt about SWTs. Respondent comments highlight visual impacts and perceptions of the efficiency of this technology are particularly important to this sector of the UK public. Taking this into careful consideration, alongside avoiding locating SWTs in contentious settings such as hedgerows and gardens where possible, may help to minimise public opposition to proposed installations. more...
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- 2016
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32. Assessments of occurrence and distribution of mammals in forests of the Garden Route National Park based on camera trapping
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Nicholas Hanekom and Rodney M. Randall
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Protected Areas ,General. Including nature conservation, geographical distribution ,QH1-199.5 - Abstract
Eleven mammal census sites were selected in four different Afrotemperate Forest types in the Garden Route National Park, South Africa. At each site, an array of eight camera traps was deployed along trails for between 28 and 45 days. Based on accumulation curves, this was generally sufficient for recording most of the focal mammal species at each site. Only 12 mammal (≥ 1 kg) species were recorded, two of which were primarily wetland species. The most widely captured taxa were bushbuck, Tragelaphus scriptus (all 11 sites); and caracal, Caracal caracal (10 sites). The most frequently photographed species were bushbuck (40%) and chacma baboon, Papio ursinus (22%). The number of species and total capture rates did not differ (P > 0.10) between dry (scrub and high) forests and moist (medium-moist to wet) forests, or between small (< 41 km²) forests and a large forest complex. However, at species level, the capture rates of caracal and vervet monkey, Chlorocebus pygerythus; were significantly lower (P ≤ 0.05) in the large forest complex than in small forests, whilst those of bushpig, Potamochoerus larvatus; were higher. Trapping cycles of between 28 and 45 days, which recorded the highest number of threatened and protected South African species, were from small forests. Conservation implications: The role of small forests in the conservation of mammals in the Garden Route National Park should be investigated further, because relatively high numbers of threatened and protected South African mammal species were recorded in these locations. more...
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- 2015
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33. E-cigarettes and smoking cessation: evidence from a systematic review and meta-analysis.
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Muhammad Aziz Rahman, Nicholas Hann, Andrew Wilson, George Mnatzaganian, and Linda Worrall-Carter
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Medicine ,Science - Abstract
E-cigarettes are currently being debated regarding their possible role in smoking cessation and as they are becoming increasingly popular, the research to date requires investigation.To investigate whether the use of e-cigarettes is associated with smoking cessation or reduction, and whether there is any difference in efficacy of e-cigarettes with and without nicotine on smoking cessation.A systematic review of articles with no limit on publication date was conducted by searching PubMed, Web of Knowledge and Scopus databases.Published studies, those reported smoking abstinence or reduction in cigarette consumption after the use of e-cigarettes, were included. Studies were systematically reviewed, and meta-analyses were conducted using Mantel-Haenszel fixed-effect and random-effects models. Degree of heterogeneity among studies and quality of the selected studies were evaluated.Six studies were included involving 7,551 participants. Meta-analyses included 1,242 participants who had complete data on smoking cessation. Nicotine filled e-cigarettes were more effective for cessation than those without nicotine (pooled Risk Ratio 2.29, 95%CI 1.05-4.97). Amongst 1,242 smokers, 224 (18%) reported smoking cessation after using nicotine-enriched e-cigarettes for a minimum period of six months. Use of such e-cigarettes was positively associated with smoking cessation with a pooled Effect Size of 0.20 (95%CI 0.11-0.28). Use of e-cigarettes was also associated with a reduction in the number of cigarettes used.Included studies were heterogeneous, due to different study designs and gender variation. Whilst we were able to comment on the efficacy of nicotine vs. non-nicotine e-cigarettes for smoking cessation, we were unable to comment on the efficacy of e-cigarettes vs. other interventions for cessation, given the lack of comparator groups in the studies included in this meta-analysis.Use of e-cigarettes is associated with smoking cessation and reduction. More randomised controlled trials are needed to assess effectiveness against other cessation methods. more...
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- 2015
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34. Electronic cigarettes: patterns of use, health effects, use in smoking cessation and regulatory issues
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Muhammad Aziz Rahman, Nicholas Hann, Andrew Wilson, and Linda Worrall-Carter
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E-cigarettes ,electronic cigarettes ,smoking ,smoking cessation ,tobacco ,Diseases of the respiratory system ,RC705-779 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Electronic cigarettes (e-cigarettes) are battery-powered devices that vaporize a liquid solution to deliver a dose of inhaled nicotine to the user. There is ongoing debate regarding their regulation. Methods This comprehensive narrative review aimed to discuss key issues including usage patterns, health effects, efficacy in smoking cessation and regulatory concerns with a view to informing future regulation and research agendas. Material and Methods PubMed, Scopus and Web of Science databases were searched using the terms (electronic cigarettes OR e-cigarettes) for articles in English, relevant to humans and published during January 2009-January 2014. Results The literature search revealed 37 relevant articles. Findings suggest that e-cigarettes are mostly used by middle-aged current smokers, particularly males, to help them for quitting or for recreation. E-cigarettes contain very low levels of multiple toxic substances such as formaldehyde and acrolein, but these levels are many times lower than those found in cigarettes. They were found to have effectiveness in aiding smoking cessation to a limited degree. Debate continues regarding regulating their use for cessation versus heavy restrictions to control recreational use on the basis that it perpetuates nicotine addiction. Conclusions The cytotoxicity and long term health effects of e-cigarettes are unknown. Nevertheless the e-cigarette market continues to expand, largely driven by middle-aged smokers who claim to be using e-cigarettes in an attempt to reduce or quit smoking. E-cigarettes may have some potential as smoking cessation aids and, in the researchers’ view, should therefore be subject to further research and regulation similar to other nicotine replacement therapies. more...
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- 2014
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35. Selection of Colloidal Silica Grouts with Respect to Gelling and Erosion Behaviour
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Pingqian Shen, Nicholas Hankins, and Stephan Jefferis
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colloidal silica ,erosion ,gel time ,gel induction time ,Geology ,QE1-996.5 - Abstract
Cembinder, Eka EXP36, and MEYCO MP320 are three colloidal silica materials that have been proposed for post-excavation grouting of deep tunnels in a radioactive waste repository. In this study, samples of these colloidal silicas were tested for their particle size distribution, gel induction time (tG), gel time (TG), and physical erosion, under mildly saline groundwater flow conditions. In order to achieve a desired gel time range, from 15 to 50 min, it is recommended that the colloidal silica is mixed with a NaCl accelerator at a 5:1 volume ratio. At 20 °C, the concentration range for the NaCl solution should be 1.5 to 1.7 M for MEYCO, 1.23 to 1.38 M for Eka EXP36, and 1.3 to 1.47 M for Cembinder. The physical erosion of the set silicas remained steady during a 10 h flow cell experiment, when grouts were subjected to 0.05 M NaCl at a superficial velocity of 2.2 × 10−5 m/s. For these test conditions, the results show that MEYCO has the highest average erosion rate (0.85 mg/h) of the three grout materials, as well as the greatest variability in this rate. Cembinder performed best with the lowest silica removal rate. Extrapolation of the measured erosion rates suggests that grout fracture dilation would not be significant under natural quiescent groundwater flow conditions, but would be high if there was hydraulic communication between the geosphere and the repository. more...
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- 2017
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36. Early cell fate decisions of human embryonic stem cells and mouse epiblast stem cells are controlled by the same signalling pathways.
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Ludovic Vallier, Thomas Touboul, Zhenzhi Chng, Minodora Brimpari, Nicholas Hannan, Enrique Millan, Lucy E Smithers, Matthew Trotter, Peter Rugg-Gunn, Anne Weber, and Roger A Pedersen
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Medicine ,Science - Abstract
Human embryonic stem cells have unique value for regenerative medicine, as they are capable of differentiating into a broad variety of cell types. Therefore, defining the signalling pathways that control early cell fate decisions of pluripotent stem cells represents a major task. Moreover, modelling the early steps of embryonic development in vitro may provide the best approach to produce cell types with native properties. Here, we analysed the function of key developmental growth factors such as Activin, FGF and BMP in the control of early cell fate decisions of human pluripotent stem cells. This analysis resulted in the development and validation of chemically defined culture conditions for achieving specification of human embryonic stem cells into neuroectoderm, mesendoderm and into extra-embryonic tissues. Importantly, these defined culture conditions are devoid of factors that could obscure analysis of developmental mechanisms or render the resulting tissues incompatible with future clinical applications. Importantly, the growth factor roles defined using these culture conditions similarly drove differentiation of mouse epiblast stem cells derived from post implantation embryos, thereby reinforcing the hypothesis that epiblast stem cells share a common embryonic identity with human pluripotent stem cells. Therefore the defined growth factor conditions described here represent an essential step toward the production of mature cell types from pluripotent stem cells in conditions fully compatible with clinical use ant also provide a general approach for modelling the early steps of mammalian embryonic development. more...
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- 2009
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