31 results on '"Jennifer Mull"'
Search Results
2. Diaphragm pacing decreases hospital charges for patients with acute cervical spinal cord injury
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David J Skarupa, Joseph Shiber, Marie L Crandall, Jennifer Mull, Andrew J Kerwin, Yohan Diaz Zuniga, Brian K Yorkgitis, Albert T Hsu, Firas G Madbak, and David J Ebler
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Surgery ,RD1-811 ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Background Cervical spinal cord injury (CSCI) is devastating and costly. Previous research has demonstrated that diaphragm pacing (DPS) is safe and improves respiratory mechanics. This may decrease hospital stays, vent days, and costs. We hypothesized DPS implantation would facilitate liberation from ventilation and would impact hospital charges.Methods We performed a retrospective review of patients with acute CSCI between January 2005 and May 2017. Routine demographics were collected. Patients underwent propensity matching based on age, injury severity score, ventilator days, hospital length of stay, and need for tracheostomy. We then adjusted total hospital charges by year using US Bureau of Labor Statistics annual adjusted Medical Care Prices. Bivariate and multivariate linear regression statistics were performed using STATA V.15.Results Between July 2011 and May 2017, all patients with acute CSCI were evaluated for DPS implantation. 40 patients who had laparoscopic DPS implantation (DPS) were matched to 61 who did not (NO DPS). Following DPS implantation, there was a statistically significant increase in spontaneous Vt compared with NO DPS (+88 mL vs −13 mL; 95% CI 46 to 131 vs −78 to 51 mL, respectively; p=0.004). Median time to liberation after DPS was significantly shorter (10 vs 29 days; 95% CI 6.5 to 13.6 vs 23.1 to 35.3 days; p
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- 2020
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3. Trauma ICU Prevalence Project: the diversity of surgical critical care
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Anne Stey, Ram Nirula, Katherine Corey, Marie Crandall, Rachel C Dirks, Thomas Schroeppel, Jeffry Nahmias, Areg Grigorian, Adrian A Maung, Jeanette Podbielski, Matthew M Carrick, Lisa M Kodadek, Chang Liu, Christopher P Michetti, Samir M Fakhry, Karen Brasel, Niels D Martin, Erik J Teicher, Anna Newcomb, Amy Stewart, Grace Chang, Michael Foreman, Evan Elizabeth Rainey, Forrest O (Dell) Moore, Jessica Huang, Krista Kaups, Rachel L Sensenig, Janika L San Roman, Clay Cothren Burlew, Eric M Campion, Len Weireter, Katherine Kelley, Dennis Kim, Erin Howell, Charles Hu, Karen Lewandowski, Elizabeth D Dauer, Kaushik Mukherjee, Liz G Penaloza, Daniel C Cullinane, Vaidehi Agrawal, Manuel Lorenzo, Dana Ferrari-Light, Michael Coomaraswamy, Michaela A West, Joseph Farhat, Karen J Brasel, Jessica H Ballou, Byron C Drumheller, Jason Radowsky, David J Dries, Elizabeth Ramey, Nicole Goulet, David H Livingston, Jonathan P Meizoso, Tanya L Zakrison, Wendy L Wahl, Mary-Margaret Brandt, Fady S Nasrallah, Kathryn B Schaffer, Joseph V Sakran, Tatiana C P Cardenas, Meenakshi Rani, Abid Khan, Elisa Moskowitz, Todd W Costantini, Jay J Doucet, Claire Pederson, Kevin H Martin, Patrick L Bosarge, Paige Farley, Jennifer Mull, Philip A Efron, Ruth Davis, Henrik Berdel, Chris Culpepper, Sonlee D West, Ashley Keiler-Green, Lily Tung, Jason L Sperry, Vincent P Anto, Milos Buhavac, Linda Ann Dultz, Lillian Kao, Reanna Adams, Javier Romero, Graal Diaz, Grant V Bochicchio, Rohit K Rasane, Casey Hill, and Andre Campbell
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Surgery ,RD1-811 ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Background Surgical critical care is crucial to the care of trauma and surgical patients. This study was designed to provide a contemporary assessment of patient types, injuries, and conditions in intensive care units (ICU) caring for trauma patients.Methods This was a multicenter prevalence study of the American Association for the Surgery of Trauma; data were collected on all patients present in participating centers’ trauma ICU (TICU) on November 2, 2017 and April 10, 2018.Results Forty-nine centers submitted data on 1416 patients. Median age was 58 years (IQR 41–70). Patient types included trauma (n=665, 46.9%), non-trauma surgical (n=536, 37.8%), medical (n=204, 14.4% overall), or unspecified (n=11). Surgical intensivists managed 73.1% of patients. Of ICU-specific diagnoses, 57% were pulmonary related. Multiple high-intensity diagnoses were represented (septic shock, 10.2%; multiple organ failure, 5.58%; adult respiratory distress syndrome, 4.38%). Hemorrhagic shock was seen in 11.6% of trauma patients and 6.55% of all patients. The most common traumatic injuries were rib fractures (41.6%), brain (38.8%), hemothorax/pneumothorax (30.8%), and facial fractures (23.7%). Forty-four percent were on mechanical ventilation, and 17.6% had a tracheostomy. One-third (33%) had an infection, and over half (54.3%) were on antibiotics. Operations were performed in 70.2%, with 23.7% having abdominal surgery. At 30 days, 5.4% were still in the ICU. Median ICU length of stay was 9 days (IQR 4–20). 30-day mortality was 11.2%.Conclusions Patient acuity in TICUs in the USA is very high, as is the breadth of pathology and the interventions provided. Non-trauma patients constitute a significant proportion of TICU care. Further assessment of the global predictors of outcome is needed to inform the education, research, clinical practice, and staffing of surgical critical care providers.Level of evidence IV, prospective observational study.
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- 2019
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4. Crystalloid Volume is Associated with Short Term Morbidity in Children with Severe Traumatic Brain Injury: An Eastern Association for the Surgery of Trauma Multicenter Trial Post-Hoc Analysis
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Taleen A. MacArthur, Adam M. Vogel, Amy E. Glasgow, Suzanne Moody, Meera Kotagal, Regan F. Williams, Mark L. Kayton, Emily C. Alberto, Randall S. Burd, Thomas J. Schroeppel, Joanne E. Baerg, Amanda Munoz, William B. Rothstein, Laura A. Boomer, Eric M. Campion, Caitlin Robinson, Rachel M. Nygaard, Chad J. Richardson, Denise I. Garcia, Christian J. Streck, Michaela Gaffley, John K. Petty, Mark Ryan, Samir Pandya, Robert T. Russell, Brian K. Yorkgitis, Jennifer Mull, Jeffrey Pence, Matthew T. Santore, Denise B. Klinkner, Shawn D. Safford, Tanya Trevilian, Aaron R. Jensen, David P. Mooney, Bavana Ketha, Melvin S. Dassinger, Anna Goldenberg-Sandau, Richard A. Falcone, and Stephanie F. Polites
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Surgery ,Critical Care and Intensive Care Medicine - Published
- 2023
5. Impact of time to surgery on mortality in hypotensive patients with noncompressible torso hemorrhage: An AAST multicenter, prospective study
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Juan Duchesne, Kevin Slaughter, Ivan Puente, John D. Berne, Brian Yorkgitis, Jennifer Mull, Jason Sperry, Matthew Tessmer, Todd Costantini, Allison E. Berndtson, Taylor Kai, Giannina Rokvic, Scott Norwood, Katelyn Meadows, Grace Chang, Brittney M. Lemon, Tomas Jacome, Lauren Van Sant, Jasmeet Paul, Zoe Maher, Amy J. Goldberg, Robert M. Madayag, Greg Pinson, Mark J. Lieser, James Haan, Gary Marshall, Matthew Carrick, and Danielle Tatum
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Injury Severity Score ,Humans ,Torso ,Surgery ,Hemorrhage ,Prospective Studies ,Hypotension ,Critical Care and Intensive Care Medicine - Abstract
Death from noncompressible torso hemorrhage (NCTH) may be preventable with improved prehospital care and shorter in-hospital times to hemorrhage control. We hypothesized that shorter times to surgical intervention for hemorrhage control would decrease mortality in hypotensive patients with NCTH.This was an AAST-sponsored multicenter, prospective analysis of hypotensive patients aged 15+ years who presented with NCTH from May 2018 to December 2020. Hypotension was defined as an initial systolic blood pressure (SBP) ≤ 90 mm Hg. Primary outcomes of interest were time to surgical intervention and in-hospital mortality.There were 242 hypotensive patients, of which 48 died (19.8%). Nonsurvivors had higher mean age (47.3 vs. 38.8; p = 0.02), higher mean New Injury Severity Score (38 vs. 29; p0.001), lower admit systolic blood pressure (68 vs. 79 mm Hg; p0.01), higher incidence of vascular injury (41.7% vs. 21.1%; p = 0.02), and shorter median (interquartile range, 25-75) time from injury to operating room start (74 minutes [48-98 minutes] vs. 88 minutes [61-128 minutes]; p = 0.03) than did survivors. Multivariable Cox regression showed shorter time from emergency department arrival to operating room start was not associated with improved survival (p = 0.04).Patients who died arrived to a trauma center in a similar time frame as did survivors but presented in greater physiological distress and had significantly shorter times to surgical hemorrhage intervention than did survivors. This suggests that even expediting a critically ill patient through the current trauma system is not sufficient time to save lives from NCTH. Civilian prehospital advance resuscitative care starting from the patient first contact needs special consideration.Prognostic/Epidemiologic, Level III.
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- 2022
6. Increased risk of malignancy for patients older than 40 years with appendicitis and an appendix wider than 10 mm on computed tomography scan: A post hoc analysis of an EAST multicenter study
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Jennifer Mull, Janika San Roman, Jason Pasley, Martin A. Schreiber, Alexis Cralley, Crystal Szczepanski, Morgan Collom, Maryam B. Tabrizi, Daniel Vazquez, Jocelyn To, Rondi B. Gelbard, Jeffrey Wild, Brandon Behrens, Ahmed E Elsharkawy, Richard D. Catalano, Elena Lita, Kaitlyn Proulx, Reginald Alouidor, D. Dante Yeh, Kailyn Kwong Hing, David C. Evans, Saskya Byerly, Victoria Sharp, Muhammad Zeeshan, David Turay, Marie Crandall, Matthew J. Bradley, Lewis E. Jacobson, Katelyn Young, Thomas Serena, Peter K. Kim, Stacie L. Allmond, Christopher M. Dodgion, Tala Kana’an, Ahmed I Eid, Jonathan M. Saxe, Savo Bou Zein Eddine, Daniel C. Cullinane, Jeffry Nahmias, Jennifer C. Roberts, Leon Naar, Steven D. Eyer, Lindsay O'Meara, Hang Zhang, Ali Fuat Kann Gok, Ryan A. Lawless, Erik J. Teicher, Bruce Long, David L. Morris, Carlos Rodriguez, Bellal Joseph, Nadine Barth, Haytham M.A. Kaafarani, Mohamed D. Ray-Zack, Georgia Vasileiou, Beatrice Sun, Victor Portillo, and Laura Juarez
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education.field_of_study ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Population ,030230 surgery ,Malignancy ,medicine.disease ,Appendix ,Confidence interval ,Appendicitis ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Relative risk ,Post-hoc analysis ,medicine ,Surgery ,Radiology ,education ,business - Abstract
Background The incidence of underlying malignancy in appendicitis ranges between 0.5% and 1.7%. We sought to identify the subset of patients with appendicitis who are at increased risk of appendiceal malignancy. Methods Using the Eastern Association for the Surgery of Trauma Multicenter Study of the Treatment of Appendicitis in America: Acute, Perforated, and Gangrenous database, we included all patients from 28 centers undergoing immediate, delayed, or interval appendectomy between 2017 and 2018. Univariate then multivariable analyses were performed to compare patients with and without malignancy and to identify independent demographic, clinical, laboratory, and/or radiological predictors of malignancy. Akaike information criteria for regression models were used to evaluate goodness of fit. Results A total of 3,293 patients were included. The median age was 38 (27–53) years, and 46.5% were female patients. On pathology, 48 (1.5%) had an underlying malignancy (adenocarcinoma [60.4%], neuroendocrine [37.5%], and lymphoma [2.1%]). Patients with malignancy were older (56 [34.5–67] vs 37 [27–52] years, P 40 years with an appendiceal diameter >10 mm on computed tomography was 2.95% compared with 0.97% in patients ≤40 years old with appendiceal diameter ≤10 mm. The corresponding risk ratio for that population was 3.03 (95% confidence interval: 1.24–7.42; P = .02). Conclusion The combination of age >40 and an appendiceal diameter >10 mm is associated with a greater than 3-fold increased risk of malignancy in patients presenting with appendicitis.
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- 2020
7. Diaphragm pacing improves respiratory mechanics in acute cervical spinal cord injury
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Firas Madbak, Yohan Diaz Zuniga, David Skarupa, Andrew J. Kerwin, Joseph Shiber, Jennifer Mull, Albert Hsu, Brian K. Yorkgitis, Marie Crandall, and David J. Ebler
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Adult ,Male ,medicine.medical_treatment ,Diaphragm ,Electric Stimulation Therapy ,Respiratory physiology ,Critical Care and Intensive Care Medicine ,law.invention ,Young Adult ,03 medical and health sciences ,Injury Severity Score ,0302 clinical medicine ,law ,Bayesian multivariate linear regression ,Humans ,Medicine ,Spinal Cord Injuries ,Retrospective Studies ,Mechanical ventilation ,business.industry ,Respiration ,Pneumonia, Ventilator-Associated ,030208 emergency & critical care medicine ,Length of Stay ,Middle Aged ,Respiration, Artificial ,Intensive care unit ,Confidence interval ,Electrodes, Implanted ,Intensive Care Units ,Diaphragm pacing ,Logistic Models ,Anesthesia ,Acute Disease ,Propensity score matching ,Cervical Vertebrae ,Linear Models ,Respiratory Mechanics ,Female ,Surgery ,Respiratory Insufficiency ,business - Abstract
BACKGROUND Cervical spinal cord injury (CSCI) is devastating with ventilator-associated pneumonia being a main driver of morbidity and mortality. Laparoscopic diaphragm pacing implantation (DPS) has been used for earlier liberation from mechanical ventilation. We hypothesized that DPS would improve respiratory mechanics and facilitate liberation. METHODS We performed a retrospective review of acute CSCI patients between January 2005 and May 2017. Routine demographics were collected. Patients underwent propensity score matching based on age, Injury Severity Score, ventilator days, hospital length of stay, and need for tracheostomy. Patients with complete respiratory mechanics data were analyzed and compared. Those who did not have DPS (NO DPS) had spontaneous tidal volume (Vt) recorded at time of intensive care unit admission, at day 7, and at day 14, and patients who had DPS had spontaneous Vt recorded before and after DPS. Time to ventilator liberation and changes in size of spontaneous Vt for patients while on the ventilator were analyzed. Bivariate and multivariate logistic and linear regression statistics were performed using STATA v10. RESULTS Between July 2011 and May 2017, 37 patients that had DPS were matched to 34 who did not (NO DPS). Following DPS, there was a statistically significant increase in spontaneous Vt compared with NO DPS (+88 mL vs. -13 mL; 95% confidence interval, 46-131 mL vs. -78 to 51 mL, respectively; p = 0.004). Median time to liberation after DPS was significantly shorter (10 days vs. 29 days; 95% CI, 6.5-13.6 days vs. 23.1-35.3 days; p < 0.001). Liberation prior to hospital discharge was not different between the two groups. The DPS placement was found to be associated with a statistically significant decrease in days to liberation and an increase in spontaneous Vt in multivariate linear regression models. CONCLUSION The DPS implantation in acute CSCI patients produces significant improvements in spontaneous Vt and reduces time to liberation from mechanical ventilation. Prospective comparative studies are needed to define the clinical benefits and potential cost savings of DPS implantation. LEVEL OF EVIDENCE Therapeutic IV.
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- 2020
8. Consolidating diverse modeling methods and spatial prioritization for multispecies connectivity planning
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Eve Bohnett, Jon Oetting, Reed Noss, Michael O’Brien, Robert Frakes, Dan Smith, Sarah Lockhart, Jennifer Mullinax, Erin E. Poor, Brian Scheick, and Thomas Hoctor
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multispecies connectivity ,spatial conservation prioritization ,corridor design ,infrastructure ,landscape conservation planning ,landscape architecture ,General. Including nature conservation, geographical distribution ,QH1-199.5 - Abstract
IntroductionGiven the different life histories and movement behaviors of diverse species, reconciling conservation measures to benefit all species is a critical concern for landscape conservation planning. Understanding land cover composition and finding multispecies movement routes across heterogeneous landscapes are crucial to maintaining many target species. The primary objectives of this study were to determine the optimal environment in Florida that promotes multispecies connectivity in landscapes increasingly threatened by rapid suburban development and to enhance methods for delineating the state’s ecological networks.MethodsPotential functional connectivity of the focal species with statewide distributions and are considered priorities because of the historical and current threats to their population viability, such as the Florida black bear (Ursus americanus floridanus), Florida panther (Puma concolor coryi), eastern indigo snake (Drymarchon couperi), and southern fox squirrel (Sciurus niger niger), were modeled using Linkage Mapper, Omniscape, and resistant kernels. We combined quantiles from each method for a single species combination approach to leverage the results from the three models for planning purposes. Subsequently, we integrated the results into a novel multiple species, multi-model connectivity mapping approach. Following the corridor analysis, a comparison was made between multispecies connectivity maps, current managed conservation lands, and the main priority areas for the Florida Wildlife Corridor, a previously developed planning network of natural hubs and corridors. Finally, we used the spatial prioritization software Zonation to identify areas of conservation priority, while also illustrating the impacts of infrastructure (built infrastructure, roadways, mining, and future development 2040 and 2070 projections) and threats from human activity (landscape fragmentation, recreation, pollution, contamination, and clean-up sites).ResultsThe study identified priority areas for all four species, with a particular focus on areas not currently protected. The connectivity models showed significant overlap with current managed conservation lands and the main priority areas for the Florida Wildlife Corridor. Pinchpoint areas or bottlenecks were identified as needing fine-scale incorporation into spatial planning. Using the spatial prioritization software Zonation, we identified areas of conservation priority and illustrated the impacts of infrastructure and threats.DiscussionThe results indicate that species-relevant connectivity models incorporating a group of focal species with both complementary and opposing habitat requirements can better inform biodiversity conservation and landscape design decisions. This multi-model approach provides a robust framework for identifying and prioritizing areas for conservation, particularly in landscapes facing rapid suburban development. Integrating multispecies connectivity models into conservation planning can enhance the effectiveness of ecological networks and contribute to the long-term viability of diverse species in Florida.
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- 2024
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9. Timing and volume of crystalloid and blood products in pediatric trauma: An Eastern Association for the Surgery of Trauma multicenter prospective observational study
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Shawn D Safford, Laura A. Boomer, David P. Mooney, Suzanne Moody, William B. Rothstein, Robert T. Russell, Stephanie F. Polites, Jeffrey C. Pence, Mark L. Kayton, Megan E. Cunningham, Eric M. Campion, Todd M. Jenkins, Randall S. Burd, Denise B. Klinkner, Tanya Trevilian, Christian J. Streck, Brian K. Yorkgitis, Cynthia Greenwell, Janika San Roman, Joanne Baerg, Taleen A. MacArthur, Bavana Ketha, Richard A. Falcone, Michaela Gaffley, Melvin S Dassinger, Jennifer Mull, Aaron R. Jensen, Alicia M. Waters, Thomas J. Schroeppel, Adam M. Vogel, Rachel M. Nygaard, Matthew T. Santore, Jessica J. Rea, Christa Black, John K. Petty, Samir Pandya, Ryan G. Spurrier, Emily C. Alberto, Denise I. Garcia, Anna Goldenberg-Sandau, Amanda Munoz, Chad J. Richardson, Regan F. Williams, Caitlin Robinson, and Bethany J. Farr
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Male ,Resuscitation ,Adolescent ,Blood Component Transfusion ,Critical Care and Intensive Care Medicine ,law.invention ,Time-to-Treatment ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Injury Severity Score ,Interquartile range ,law ,Intensive care ,Medicine ,Humans ,Hospital Mortality ,Prospective Studies ,Child ,business.industry ,Infant ,030208 emergency & critical care medicine ,Emergency department ,Crystalloid Solutions ,medicine.disease ,Intensive care unit ,United States ,Anesthesia ,Child, Preschool ,Wounds and Injuries ,Surgery ,Female ,business ,Pediatric trauma - Abstract
BACKGROUND The purpose of this study was to determine the relationship between timing and volume of crystalloid before blood products and mortality, hypothesizing that earlier transfusion and decreased crystalloid before transfusion would be associated with improved outcomes. METHODS A multi-institutional prospective observational study of pediatric trauma patients younger than 18 years, transported from the scene of injury with elevated age-adjusted shock index on arrival, was performed from April 2018 to September 2019. Volume and timing of prehospital, emergency department, and initial admission resuscitation were assessed including calculation of 20 ± 10 mL/kg crystalloid boluses overall and before transfusion. Multivariable Cox proportional hazards and logistic regression models identified factors associated with mortality and extended intensive care, ventilator, and hospital days. RESULTS In 712 children at 24 trauma centers, mean age was 7.6 years, median (interquartile range) Injury Severity Score was 9 (2-20), and in-hospital mortality was 5.3% (n = 38). There were 311 patients(43.7%) who received at least one crystalloid bolus and 149 (20.9%) who received blood including 65 (9.6%) with massive transfusion activation. Half (53.3%) of patients who received greater than one crystalloid bolus required transfusion. Patients who received blood first (n = 41) had shorter median time to transfusion (19.8 vs. 78.0 minutes, p = 0.005) and less total fluid volume (50.4 vs. 86.6 mL/kg, p = 0.033) than those who received crystalloid first despite similar Injury Severity Score (median, 22 vs. 27, p = 0.40). On multivariable analysis, there was no association with mortality (p = 0.51); however, each crystalloid bolus after the first was incrementally associated with increased odds of extended ventilator, intensive care unit, and hospital days (all p < 0.05). Longer time to transfusion was associated with extended ventilator duration (odds ratio, 1.11; p = 0.04). CONCLUSION Resuscitation with greater than one crystalloid bolus was associated with increased need for transfusion and worse outcomes including extended duration of mechanical ventilation and hospitalization in this prospective study. These data support a crystalloid-sparing, early transfusion approach for resuscitation of injured children. LEVEL OF EVIDENCE Therapeutic, level IV.
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- 2020
10. Resuscitative Endovascular Balloon Occlusion of the Aorta and Resuscitative Thoracotomy in Select Patients with Hemorrhagic Shock: Early Results from the American Association for the Surgery of Trauma's Aortic Occlusion in Resuscitation for Trauma and Acute Care Surgery Registry
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Chad G. Ball, Karen Herzing, Todd E. Rasmussen, Joseph J. DuBose, Joseph Skaja, Jennifer Knight, Jennifer Mull, Xian Luo-Owen, Alberto Aiolfi, Michael Long, Nam T. Tran, Matthew B. Bloom, Elizabeth Dauer, Chad J. Richardson, Rachel M. Nygaard, Jeanette M. Podbielski, Andrew W. Kirkpatrick, William A. Teeter, David Skarupa, Eileen M. Bulger, Nicole Cornell, David Turay, Stephanie Gordy, Kenji Inaba, Joshua Pringle, Douglas Johnson, Joseph A Ibrahim, Timothy C. Fabian, Philip J. Wasicek, Tiffany K. Bee, Laura J. Moore, Thomas M. Scalea, Cassra N. Arbabi, Sarah Matthew, Scott T. Trexler, Kailey Nolan, Jeremy W. Cannon, Shahram Aarabi, Sonya Charo-Griego, John B. Holcomb, Karen Safcsak, John K. Bini, Zhengwen Xiao, Megan Brenner, Nathaniel Poulin, Joannis Baez Gonzalez, John H. Matsuura, and Jeannette G. Ward
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Adult ,Male ,medicine.medical_specialty ,Resuscitation ,Thoracic Injuries ,Aorta, Thoracic ,Shock, Hemorrhagic ,030230 surgery ,03 medical and health sciences ,Injury Severity Score ,0302 clinical medicine ,Interquartile range ,medicine.artery ,medicine ,Humans ,Thoracic aorta ,Prospective Studies ,Survival rate ,Resuscitative thoracotomy ,business.industry ,Glasgow Coma Scale ,030208 emergency & critical care medicine ,Emergency department ,Balloon Occlusion ,Middle Aged ,United States ,Surgery ,Survival Rate ,Treatment Outcome ,Thoracotomy ,Female ,business - Abstract
Aortic occlusion is a potentially valuable tool for early resuscitation in patients nearing extremis or in arrest from severe hemorrhage.The American Association for the Surgery of Trauma's Aortic Occlusion in Resuscitation for Trauma and Acute Care Surgery registry identified trauma patients without penetrating thoracic injury undergoing aortic occlusion at the level of the descending thoracic aorta (resuscitative thoracotomy [RT] or zone 1 resuscitative endovascular balloon occlusion of the aorta [REBOA]) in the emergency department (ED). Survival outcomes relative to the timing of CPR need and admission hemodynamic status were examined.Two hundred and eighty-five patients were included: 81.8% were males, with injury due to penetrating mechanisms in 41.4%; median age was 35.0 years (interquartile range 29 years) and median Injury Severity Score was 34.0 (interquartile range 18). Resuscitative thoracotomy was used in 71%, and zone 1 REBOA in 29%. Overall survival beyond the ED was 50% (RT 44%, REBOA 63%; p = 0.004) and survival to discharge was 5% (RT 2.5%, REBOA 9.6%; p = 0.023). Discharge Glasgow Coma Scale score was 15 in 85% of survivors. Prehospital CPR was required in 60% of patients with a survival beyond the ED of 37% and survival to discharge of 3% (all p0.05). Patients who did not require any CPR before had a survival beyond the ED of 70% (RT 48%, REBOA 93%; p0.001) and survival to discharge of 13% (RT 3.4%, REBOA 22.2%, p = 0.048). If aortic occlusion patients did not require CPR but presented with hypotension (systolic blood pressure90 mmHg; 9% [65% RT; 35% REBOA]), they achieved survival beyond the ED in 65% (p = 0.009) and survival to discharge of 15% (RT 0%, REBOA 44%; p = 0.008).Overall, REBOA can confer a survival benefit over RT, particularly in patients not requiring CPR. Considerable additional study is required to definitively recommend REBOA for specific subsets of injured patients.
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- 2018
11. Does Clamshell Thoracotomy Better Facilitate Thoracic Life-Saving Procedures Without Increased Complication Compared with an Anterolateral Approach to Resuscitative Thoracotomy? Results from the American Association for the Surgery of Trauma Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery Registry
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Laura J. Moore, Kathryn Johnson, Jeannette G. Ward, John K. Bini, Timothy W. Wolff, Robert M. Madayag, Thomas M. Scalea, Nicole Cornell, Alice Piccinini, Forrest 'Dell' Moore, Chad J. Richardson, Zhengwen Xiao, Yohan Diaz Zuniga, David Turay, Valorie L. Baggenstoss, Matthew Yanoff, Xian Luo-Owen, Ernest E. Moore, David V. Feliciano, Stephanie Gordy, Reagan Bollig, Rachele Solomon, Brian J. Daley, Mark J. Seamon, Jonathan J. Morrison, Joseph A Ibrahim, Juan C. Quispe, Jeanette M. Podbielski, Chance Spalding, Elizabeth Warnack, Nathaniel Poulin, Catherine Rauschendorfer, John H. Matsuura, Jennifer Knight, Joseph Farhat, Marko Bukur, Joshua Pringle, John B. Holcomb, Karen Herzing, Joseph J. DuBose, Derek Lumbard, David Skarupa, Chad G. Ball, Kailey Nolan, Jeremy W. Cannon, Andrew W. Kirkpatrick, Kenji Inaba, Jennifer Mull, Rachel M. Nygaard, Matthew B. Bloom, Elizabeth Dauer, Dafney Davare, Nam T. Tran, Seong Lee, Karen Safcsak, Eileen M. Bulger, Niki Rasnake, David S. Kauvar, William A. Teeter, Charles J. Fox, and Pamela Bourg
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Adult ,Male ,Resuscitation ,medicine.medical_specialty ,medicine.medical_treatment ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,medicine.artery ,Humans ,Medicine ,Registries ,Thoracotomy ,Aorta ,Lung ,Resuscitative thoracotomy ,business.industry ,Balloon Occlusion ,Survival Analysis ,Surgery ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Wounds and Injuries ,Injury Severity Score ,Female ,030211 gastroenterology & hepatology ,business ,Complication - Abstract
Background Resuscitative thoracotomy (RT) is life-saving in select patients and can be accomplished through a left anterolateral (AT) or clamshell thoracotomy (CT). CT may provide additional exposure, facilitating certain operative procedures, but the added blood and heat loss and time to perform it may increase complications. No prospective multicenter comparison of techniques has yet been reported. Study Design The observational AAST Aortic Occlusion for Resuscitation in Trauma and Acute care surgery (AORTA) registry was used to compare AT and CT in RT. Results AORTA recorded 1,218 RTs at 46 trauma centers from June 2014 to January 2020. Overall survival after RT was 6.0% (AT 6.6%; [59 of 900]; CT 4.2% [13 of 296], p = 0.132). Among all RTs, 11.1% (142 of 1,278) surviving at least 24 hours were used tocompare AT (112) and CT (30). There was no difference between the 2 groups withregard to age, sex, Injury Severity Score, or mechanism of injury (Table 1). CT was significantly more likely to be used in patients needing resection of the lung or cardiac repair. CT was not associated with increased local thoracic/systemic complications, higher transfusion requirement, or greater ventilator, ICU, or hospital days compared with AT. Conclusions Clamshell thoracotomy facilitates thoracic life-saving procedures withoutincreased systemic or thoracic complications compared with AT in patients undergoing RT.
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- 2020
12. Second-Trimester Dilation and Evacuation: A Simulation-Based Team Training Curriculum
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Leah N. Schwartz, Andrea Pelletier, Alisa B. Goldberg, Kari Braaten, Brian Donnenfeld, Jennifer Muller, Persephone Giannarikas, Nancy Falconer, Deborah Campbell, and Deborah Bartz
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Abortion ,Dilation & Evacuation ,Intrauterine Fetal Demise ,Hemorrhage ,OB/GYN ,Simulation ,Medicine (General) ,R5-920 ,Education - Abstract
Introduction Despite the need for providers skilled in second-trimester dilation and evacuation (D&E) procedures, there are few second-trimester abortion training opportunities for OB/GYN residents and other health care trainees. Barriers to such training include restrictive state laws and institutional policies, lack of trained faculty, and limited procedural volume. Simulation-based D&E training is, therefore, a critical tool for OB/GYN residents and other medical professionals to achieve clinical competency. Methods This simulation for OB/GYN residents centers on a 29-year-old woman at 18 weeks gestation with intrauterine fetal demise, requiring learners to perform a second-trimester D&E and manage an unexpected postprocedural hemorrhage. We designed the simulation to be used with a high-fidelity mannequin. Personnel roles required for the simulation included an anesthesiologist, medical assistant, OR nurse, and two OB/GYN faculty. Learner performance was assessed using a pre- and postsimulation learner evaluation, a critical action checklist, and a focus group with simulation facilitators. Results Forty-nine residents participated over an 8-year period. Learners demonstrated improved competency performing a second-trimester D&E and increased confidence managing postprocedural hemorrhage after participating in this simulation. In addition, focus group participants reported that a majority of learners demonstrated confidence and effective communication with team members while performing in a decision-making role. Discussion In addition to improving learners’ clinical competency and surgical confidence for second-trimester D&E procedures, this simulation serves as a valuable instrument for the standardized assessment of learners’ performance, as well as an opportunity for all participants to practice teamwork and communication in a high-acuity setting.
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- 2023
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13. Structure, Function and Pharmacology of SLC7 Family Members and Homologues
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Jean-Marc Jeckelmann, Jonas Zaugg, Veronika Morozova, Jennifer Müller, Satish Kantipudi, Mariana Schroeder, Julien Graff, Christiane Albrecht, Karl-Heinz Altmann, Jürg Gertsch, and Dimitrios Fotiadis
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Amino acid transporter ,Inhibitor ,LAT1 ,LAT2 ,SLC7 ,Chemistry ,QD1-999 - Abstract
Amino acids are essential components of all living cells serving as building blocks of proteins, as energy source, and as precursors of metabolites and signaling molecules. Amino acid transporters are membrane proteins that mediate the transfer of amino acids across the plasma membrane, and between compartments in cells, different cells and organs. The absence, overexpression or malfunction of specific amino acid transporters have been associated with human disease. One of the projects within the Swiss National Centre of Competence in Research (NCCR) TransCure was directed at SLC7 family amino acid transporters, with a particular focus on the heteromeric amino acid transporters 4F2hc-LAT1 (SLC3A2-SLC7A5) and 4F2hc-LAT2 (SLC3A2-SLC7A8), and the bacterial homologue AdiC. The project addressed questions of basic research (function and structure), pharmacology (identification of potent inhibitors and activators), and pre-clinical medicine (e.g., physiological role in the placenta) and disease models (e.g., tumor progression) of specific SLC7 family amino acid transporters. This review presents, summarizes and discusses selected main results obtained in this NCCR TransCure project.
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- 2022
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14. Mechanism of substrate transport and inhibition of the human LAT1-4F2hc amino acid transporter
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Renhong Yan, Yaning Li, Jennifer Müller, Yuanyuan Zhang, Simon Singer, Lu Xia, Xinyue Zhong, Jürg Gertsch, Karl-Heinz Altmann, and Qiang Zhou
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Cytology ,QH573-671 - Abstract
Abstract LAT1 (SLC7A5) is one of the representative light chain proteins of heteromeric amino acid transporters, forming a heterodimer with its heavy chain partner 4F2hc (SLC3A2). LAT1 is overexpressed in many types of tumors and mediates the transfer of drugs and hormones across the blood-brain barrier. Thus, LAT1 is considered as a drug target for cancer treatment and may be exploited for drug delivery into the brain. Here, we synthesized three potent inhibitors of human LAT1, which inhibit transport of leucine with IC50 values between 100 and 250 nM, and solved the cryo-EM structures of the corresponding LAT1-4F2hc complexes with these inhibitors bound at resolution of up to 2.7 or 2.8 Å. The protein assumes an outward-facing occluded conformation, with the inhibitors bound in the classical substrate binding pocket, but with their tails wedged between the substrate binding site and TM10 of LAT1. We also solved the complex structure of LAT1-4F2hc with 3,5-diiodo-l-tyrosine (Diiodo-Tyr) at 3.4 Å overall resolution, which revealed a different inhibition mechanism and might represent an intermediate conformation between the outward-facing occluded state mentioned above and the outward-open state. To our knowledge, this is the first time that the outward-facing conformation is revealed for the HAT family. Our results unveil more important insights into the working mechanisms of HATs and provide a structural basis for future drug design.
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- 2021
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15. Resting-State Functional MRI Metrics in Patients With Chronic Mild Traumatic Brain Injury and Their Association With Clinical Cognitive Performance
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Faezeh Vedaei, Andrew B. Newberg, Mahdi Alizadeh, Jennifer Muller, Shiva Shahrampour, Devon Middleton, George Zabrecky, Nancy Wintering, Anthony J. Bazzan, Daniel A. Monti, and Feroze B. Mohamed
- Subjects
traumatic brain injury ,resting-state functional magnetic resonance imaging ,fractional amplitude of low-frequency fluctuation ,regional homogeneity ,functional connectivity ,cognitive performance ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Mild traumatic brain injury (mTBI) accounts for more than 80% of people experiencing brain injuries. Symptoms of mTBI include short-term and long-term adverse clinical outcomes. In this study, resting-state functional magnetic resonance imaging (rs-fMRI) was conducted to measure voxel-based indices including fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) in patients suffering from chronic mTBI; 64 patients with chronic mTBI at least 3 months post injury and 40 healthy controls underwent rs-fMRI scanning. Partial correlation analysis controlling for age and gender was performed within mTBI cohort to explore the association between rs-fMRI metrics and neuropsychological scores. Compared with controls, chronic mTBI patients showed increased fALFF in the left middle occipital cortex (MOC), right middle temporal cortex (MTC), and right angular gyrus (AG), and increased ReHo in the left MOC and left posterior cingulate cortex (PCC). Enhanced FC was observed from left MOC to right precuneus; from right MTC to right superior temporal cortex (STC), right supramarginal, and left inferior parietal cortex (IPC); and from the seed located at right AG to left precuneus, left superior medial frontal cortex (SMFC), left MTC, left superior temporal cortex (STC), and left MOC. Furthermore, the correlation analysis revealed a significant correlation between neuropsychological scores and fALFF, ReHo, and seed-based FC measured from the regions with significant group differences. Our results demonstrated that alterations of low-frequency oscillations in chronic mTBI could be representative of disruption in emotional circuits, cognitive performance, and recovery in this cohort.
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- 2021
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16. Comprehensive phenotypic analysis of the Dp1Tyb mouse strain reveals a broad range of Down syndrome-related phenotypes
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Eva Lana-Elola, Heather Cater, Sheona Watson-Scales, Simon Greenaway, Jennifer Müller-Winkler, Dorota Gibbins, Mihaela Nemes, Amy Slender, Tertius Hough, Piia Keskivali-Bond, Cheryl L. Scudamore, Eleanor Herbert, Gareth T. Banks, Helene Mobbs, Tara Canonica, Justin Tosh, Suzanna Noy, Miriam Llorian, Patrick M. Nolan, Julian L. Griffin, Mark Good, Michelle Simon, Ann-Marie Mallon, Sara Wells, Elizabeth M. C. Fisher, and Victor L. J. Tybulewicz
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down syndrome ,mouse model ,craniofacial development ,memory ,sleep ,hearing ,diabetes ,haematopoiesis ,Medicine ,Pathology ,RB1-214 - Abstract
Down syndrome (DS), trisomy 21, results in many complex phenotypes including cognitive deficits, heart defects and craniofacial alterations. Phenotypes arise from an extra copy of human chromosome 21 (Hsa21) genes. However, these dosage-sensitive causative genes remain unknown. Animal models enable identification of genes and pathological mechanisms. The Dp1Tyb mouse model of DS has an extra copy of 63% of Hsa21-orthologous mouse genes. In order to establish whether this model recapitulates DS phenotypes, we comprehensively phenotyped Dp1Tyb mice using 28 tests of different physiological systems and found that 468 out of 1800 parameters were significantly altered. We show that Dp1Tyb mice have wide-ranging DS-like phenotypes, including aberrant erythropoiesis and megakaryopoiesis, reduced bone density, craniofacial changes, altered cardiac function, a pre-diabetic state, and deficits in memory, locomotion, hearing and sleep. Thus, Dp1Tyb mice are an excellent model for investigating complex DS phenotype-genotype relationships for this common disorder.
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- 2021
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17. Polygenic risk scores differentiate schizophrenia patients with toxoplasma gondii compared to toxoplasma seronegative patients
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Adriana Lori, Dimitrios Avramopoulos, Alex W. Wang, Jennifer Mulle, Nicholas Massa, Erica J. Duncan, Abigail Powers, Karen Conneely, Charles F. Gillespie, Tanja Jovanovic, Kerry J. Ressler, and Brad D. Pearce
- Subjects
Psychiatry ,RC435-571 - Abstract
Schizophrenia (SCZ) is an etiologically heterogeneous disease with genetic and environmental risk factors (e.g., Toxoplasma gondii infection) differing among affected individuals. Distinguishing such risk factors may point to differences in pathophysiological pathways and facilitate the discovery of individualized treatments. Toxoplasma gondii (TOXO) has been implicated in increasing the risk of schizophrenia. To determine whether TOXO-positive individuals with SCZ have a different polygenic risk burden than uninfected people, we applied the SCZ polygenic risk score (SCZ-PRS) derived from the Psychiatric GWAS Consortium separately to the TOXO-positive and TOXO-negative subjects with the diagnosis of SCZ as the outcome variable. The SCZ-PRS does not include variants in the major histocompatibility complex.Of 790 subjects assessed for TOXO, the 662 TOXO-negative subjects (50.8% with SCZ) reached a Bonferroni corrected significant association (p = 0.00017, R2 = 0.023). In contrast, the 128 TOXO-positive individuals (53.1% with SCZ) showed no significant association (p = 0.354) for SCZ-PRS and had a much lower R2 (R2 = 0.007). To account for Type-2 error in the TOXO-positive dataset, we performed a random sampling of the TOXO-negative subpopulation (n = 130, repeated 100 times) to simulate equivalent power between groups: the p-value was 0.354.We found intriguing evidence that the SCZ-PRS predicts SCZ in TOXO-negative subjects, as expected, but not in the TOXO-positive individuals. This result highlights the importance of considering environmental risk factors to distinguish a subgroup with independent or different genetic components involved in the development of SCZ.
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- 2021
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18. Protocol for the Emory University African American maternal stress and infant gut microbiome cohort study
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Patricia A. Brennan, Anne L. Dunlop, Alicia K. Smith, Michael Kramer, Jennifer Mulle, and Elizabeth J. Corwin
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Stress ,Perinatal ,Microbiome ,Infant ,Neurodevelopment ,Pediatrics ,RJ1-570 - Abstract
Abstract Background The microbial population of the human gut (the gut microbiome) is an integral cog in the bidirectional communication axis that exists between the gastrointestinal tract and the central nervous system. African American infants disproportionately experience multiple, overlapping vulnerabilities such as preterm birth and formula rather than breast feeding that may disrupt the development of the infant microbiome. African American infants also are more likely to have mothers affected by chronic stress both pre- and post-natally. Perhaps relatedly, African American offspring are disproportionately affected by neurodevelopmental delays. Taken together, these findings suggest that one important mechanism that may link prenatal and postnatal stress and African American infant brain development is the composition of the infant microbiome. Methods In our ongoing longitudinal study, Maternal Stress and the Gut-Brain Axis in African American Infants (R01MD009746), we investigate associations between maternal prenatal and postnatal stress and the composition of the infant gut microbiome, in relation to cognitive and social-emotional development. We aim to recruit 300 African American mother-infant dyads, contingent on the mother’s previous participation in an associated prenatal cohort study: Biobehavioral Determinants of the Microbiome and Preterm Birth in Black Women (R01NR014800). Following enrollment, we assess infants at 1-week, and 3-, 6-, 12-and 18-months to collect: standardized assessments of infant neurocognitive and social-emotional development; questionnaire measures of infant feeding and health; observational data on maternal-infant interactions; maternal reports of postnatal stress; blood and saliva samples to evaluate maternal and infant psychoneuroimmunologic (PNI) function; and infant stool samples to characterize acquisition and trajectory of gut microbiome composition. Genetic variants of the major histocompatibility complex that may influence gut microbiome composition are also being evaluated. Discussion This rich data set will allow future consideration of risk and protective factors that influence neurodevelopment in African American infants who are exposed to varying levels of prenatal and early life stress. Evidence for a mechanistic role of the microbiome would provide a framework for future clinical evaluations of preventative interventions (e.g., probiotics, culturally-appropriate breastfeeding campaigns) that could potentially improve the health and development of African American children in infancy and across the lifespan.
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- 2019
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19. Hybrid diffusion imaging reveals altered white matter tract integrity and associations with symptoms and cognitive dysfunction in chronic traumatic brain injury
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Jennifer Muller, Devon Middleton, Mahdi Alizadeh, George Zabrecky, Nancy Wintering, Anthony J. Bazzan, Ji Lang, Chengyuan Wu, Daniel A. Monti, Qianhong Wu, Andrew B. Newberg, and Feroze B. Mohamed
- Subjects
Traumatic brain injury ,Hybrid diffusion imaging ,Post-concussion syndrome ,Diffusion tensor imaging ,Neurite orientation dispersion and density imaging ,Multi-band imaging ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
The detection and association of in vivo biomarkers in white matter (WM) pathology after acute and chronic mild traumatic brain injury (mTBI) are needed to improve care and develop therapies. In this study, we used the diffusion MRI method of hybrid diffusion imaging (HYDI) to detect white matter alterations in patients with chronic TBI (cTBI). 40 patients with cTBI presenting symptoms at least three months post injury, and 17 healthy controls underwent magnetic resonance HYDI. cTBI patients were assessed with a battery of neuropsychological tests. A voxel-wise statistical analysis within the white matter skeleton was performed to study between group differences in the diffusion models. In addition, a partial correlation analysis controlling for age, sex, and time after injury was performed within the cTBI cohort, to test for associations between diffusion metrics and clinical outcomes. The advanced diffusion modeling technique of neurite orientation dispersion and density imaging (NODDI) showed large clusters of between-group differences resulting in lower values in the cTBI across the brain, where the single compartment diffusion tensor model failed to show any significant results. However, the diffusion tensor model appeared to be just as sensitive in detecting self-reported symptoms in the cTBI population using a within-group correlation. To the best of our knowledge this study provides the first application of HYDI in evaluation of cTBI using combined DTI and NODDI, significantly enhancing our understanding of the effects of concussion on white matter microstructure and emphasizing the utility of full characterization of complex diffusion to diagnose, monitor, and treat brain injury.
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- 2021
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20. The B-cell inhibitory receptor CD22 is a major factor in host resistance to Streptococcus pneumoniae infection.
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Vitor E Fernandes, Giuseppe Ercoli, Alan Bénard, Carolin Brandl, Hannah Fahnenstiel, Jennifer Müller-Winkler, Georg F Weber, Paul Denny, Lars Nitschke, and Peter W Andrew
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Streptococcus pneumoniae is a major human pathogen, causing pneumonia and sepsis. Genetic components strongly influence host responses to pneumococcal infections, but the responsible loci are unknown. We have previously identified a locus on mouse chromosome 7 from a susceptible mouse strain, CBA/Ca, to be crucial for pneumococcal infection. Here we identify a responsible gene, Cd22, which carries a point mutation in the CBA/Ca strain, leading to loss of CD22 on B cells. CBA/Ca mice and gene-targeted CD22-deficient mice on a C57BL/6 background are both similarly susceptible to pneumococcal infection, as shown by bacterial replication in the lungs, high bacteremia and early death. After bacterial infections, CD22-deficient mice had strongly reduced B cell populations in the lung, including GM-CSF producing, IgM secreting innate response activator B cells, which are crucial for protection. This study provides striking evidence that CD22 is crucial for protection during invasive pneumococcal disease.
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- 2020
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21. Moved by Emotions: Affective Concepts Representing Personal Life Events Induce Freely Performed Steps in Line With Combined Sagittal and Lateral Space-Valence Associations
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Susana Ruiz Fernández, Lydia Kastner, Sergio Cervera-Torres, Jennifer Müller, and Peter Gerjets
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bodily resonance ,personal life events ,space-valence associations ,approach-avoidance behaviors ,Body Specificity Hypothesis ,free-choice directional step paradigm ,Psychology ,BF1-990 - Abstract
Embodiment approaches to cognition and emotion have put forth the idea that the way we think and talk about affective events often recruits spatial information that stems, to some extent, from our bodily experiences. For example, metaphorical expressions such as “being someone’s right hand” or “leaving something bad behind” convey affectivity associated with the lateral and sagittal dimensions of space. Action tendencies associated with affect such as the directional fluency of hand movements (dominant right hand-side – positive; non-dominant left hand-side – negative) and approach-avoidance behaviors (forward – positive; backwards – negative) might be mechanisms supporting such associations. Against this background, experimental research has investigated whether positive and negative words are freely allocated into space (e.g., close or far from one’s body) or resonate with congruent (vs. incongruent) predefined manual actions usually performed by joysticks or button presses (e.g., positive – right; negative – left, or vice versa). However, to date, it is unclear how the processing of affective concepts resonate with directional actions of the whole body, the more if such actions are performed freely within a context enabling both, lateral and sagittal movements. Accordingly, 67 right-handed participants were to freely step on an 8-response pad (front, back, right, left, front-right, front-left, back-right, or back-left) after being presented in front of them valence-laden personal life-events submitted before the task (e.g., words or sentences such as “graduation” or “birth of a child”). The most revealing finding of this study indicates that approach-avoidance behaviors and space-valence associations across laterality are interwoven during whole body step actions: Positive events induced steps highly biased to front-right whereas negative events induced steps highly biased to back-left.
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- 2019
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22. Stability of the vaginal, oral, and gut microbiota across pregnancy among African American women: the effect of socioeconomic status and antibiotic exposure
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Anne L. Dunlop, Anna K. Knight, Glen A. Satten, Anya J. Cutler, Michelle L. Wright, Rebecca M. Mitchell, Timothy D. Read, Jennifer Mulle, Vicki S. Hertzberg, Cherie C. Hill, Alicia K. Smith, and Elizabeth J. Corwin
- Subjects
Microbiome ,Microbiota ,Pregnancy ,Social class ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Objective A growing body of research has investigated the human microbiota and pregnancy outcomes, especially preterm birth. Most studies of the prenatal microbiota have focused on the vagina, with fewer investigating other body sites during pregnancy. Although pregnancy involves profound hormonal, immunological and metabolic changes, few studies have investigated either shifts in microbiota composition across pregnancy at different body sites or variation in composition at any site that may be explained by maternal characteristics. The purpose of this study was to investigate: (1) the stability of the vaginal, oral, and gut microbiota from early (8–14 weeks) through later (24–30 weeks) pregnancy among African American women according to measures of socioeconomic status, accounting for prenatal antibiotic use; (2) whether measures of socioeconomic status are associated with changes in microbiota composition over pregnancy; and (3) whether exposure to prenatal antibiotics mediate any observed associations between measures of socioeconomic status and stability of the vaginal, oral, and gut microbiota across pregnancy. Methods We used paired vaginal, oral, or gut samples available for 16S rRNA gene sequencing from two time points in pregnancy (8–14 and 24–30 weeks) to compare within-woman changes in measures of alpha diversity (Shannon and Chao1) and beta-diversity (Bray–Curtis dissimilarity) among pregnant African American women (n = 110). Multivariable linear regression was used to examine the effect of level of education and prenatal health insurance as explanatory variables for changes in diversity, considering antibiotic exposure as a mediator, adjusting for age, obstetrical history, and weeks between sampling. Results For the oral and gut microbiota, there were no significant associations between measures of socioeconomic status or prenatal antibiotic use and change in Shannon or Chao1 diversity. For the vaginal microbiota, low level of education (high school or less) was associated with an increase in Shannon and Chao1 diversity over pregnancy, with minimal attenuation when controlling for prenatal antibiotic use. Conversely, for within-woman Bray–Curtis dissimilarity for early compared to later pregnancy, low level of education and prenatal antibiotics were associated with greater dissimilarity for the oral and gut sites, with minimal attenuation when controlling for prenatal antibiotics, and no difference in dissimilarity for the vaginal site. Conclusions Measures of maternal socioeconomic status are variably associated with changes in diversity across pregnancy for the vaginal, oral, and gut microbiota, with minimal attenuation by prenatal antibiotic exposure. Studies that evaluate stability of the microbiota across pregnancy in association with health outcomes themselves associated with socioeconomic status (such as preterm birth) should incorporate measures of socioeconomic status to avoid finding spurious relationships.
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- 2019
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23. Regulatory, Legal, and Market Aspects of Smart Wearables for Cardiac Monitoring
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Jan Benedikt Brönneke, Jennifer Müller, Konstantinos Mouratis, Julia Hagen, and Ariel Dora Stern
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medical devices ,regulation ,market access ,smart wearables ,Chemical technology ,TP1-1185 - Abstract
In the area of cardiac monitoring, the use of digitally driven technologies is on the rise. While the development of medical products is advancing rapidly, allowing for new use-cases in cardiac monitoring and other areas, regulatory and legal requirements that govern market access are often evolving slowly, sometimes creating market barriers. This article gives a brief overview of the existing clinical studies regarding the use of smart wearables in cardiac monitoring and provides insight into the main regulatory and legal aspects that need to be considered when such products are intended to be used in a health care setting. Based on this brief overview, the article elaborates on the specific requirements in the main areas of authorization/certification and reimbursement/compensation, as well as data protection and data security. Three case studies are presented as examples of specific market access procedures: the USA, Germany, and Belgium. This article concludes that, despite the differences in specific requirements, market access pathways in most countries are characterized by a number of similarities, which should be considered early on in product development. The article also elaborates on how regulatory and legal requirements are currently being adapted for digitally driven wearables and proposes an ongoing evolution of these requirements to facilitate market access for beneficial medical technology in the future.
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- 2021
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24. Protocol for the Emory University African American Vaginal, Oral, and Gut Microbiome in Pregnancy Cohort Study
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Elizabeth J. Corwin, Carol J. Hogue, Bradley Pearce, Cherie C. Hill, Timothy D. Read, Jennifer Mulle, and Anne L. Dunlop
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Microbiome ,Chronic stress ,Preterm birth ,Pregnancy ,Health disparity ,Gynecology and obstetrics ,RG1-991 - Abstract
Abstract Background Adverse birth and neonatal outcomes disproportionately affect African American women and infants compared to those of other races/ethnicities. While significant research has sought to identify underlying factors contributing to these disparities, current understanding remains limited, constraining prevention, early diagnosis, and treatment. With the development of next generation sequencing techniques, the contribution of the vaginal microbiome to adverse maternal and neonatal outcomes has come under consideration. However, most microbiome in pregnancy studies include few African American women, do not consider the potential contribution of non-vaginal microbiome sites, and do not consider the effects of sociodemographic or behavioral factors on the microbiome. Methods We conceived our on-going, 5-year longitudinal study, Biobehavioral Determinants of the Microbiome and Preterm Birth in Black Women, as an intra-race study to enable the investigation of risk and protective factors within the disparate group. We aim to recruit over 500 pregnant African American women, enrolling them into the study at 8–14 weeks of pregnancy. Participants will be asked to complete questionnaires and provide oral, vaginal, and gut microbiome samples at enrollment and again at 24–30 weeks. Chart review will be used to identify pregnancy outcomes, infections, treatments, and complications. DNA will be extracted from the microbiome samples and sequencing of the V3 and V4 regions of the 16S rRNA gene will be conducted. Processing and mapping will be completed with QIIME and operational taxonomic units (OTUs) will be mapped to Greengenes version 13_8. Community state types (CSTs) and diversity measures at each site and time will be identified and considered in light of demographic, psychosocial, clinical, and biobehavioral variables. Discussion This rich data set will allow future consideration of risk and protective factors, between and within groups of women, providing the opportunity to uncover the roots of the persistent health disparity experienced by African American families.
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- 2017
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25. Not so Dangerous After All? Venom Composition and Potency of the Pholcid (Daddy Long-Leg) Spider Physocyclus mexicanus
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Pamela A. Zobel-Thropp, Jennifer Mullins, Charles Kristensen, Brent A. Kronmiller, Cynthia L. David, Linda A. Breci, and Greta J. Binford
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neprilysin ,astacin metalloproteinase ,insecticidal neurotoxin ,proteome ,PD50 ,Evolution ,QH359-425 ,Ecology ,QH540-549.5 - Abstract
Pholcid spiders (Araneae: Pholcidae), officially “cellar spiders” but popularly known as “daddy long-legs,” are renown for the potential of deadly toxic venom, even though venom composition and potency has never formally been studied. Here we detail the venom composition of male Physocyclus mexicanus using proteomic analyses and venom-gland transcriptomes (“venomics”). We also analyze the venom's potency on insects, and assemble available evidence regarding mammalian toxicity. The majority of the venom (51% of tryptic polypeptides and 62% of unique tryptic peptides) consists of proteins homologous to known venom toxins including enzymes (astacin metalloproteases, serine proteases and metalloendopeptidases, particularly neprilysins) and venom peptide neurotoxins. We identify 17 new groups of peptides (U1−17-PHTX) most of which are homologs of known venom peptides and are predicted to have an inhibitor cysteine knot fold; of these, 13 are confirmed in the proteome. Neprilysins (M13 peptidases), and astacins (M12 peptidases) are the most abundant venom proteins, respectively representing 15 and 11% of the individual proteins and 32 and 20% of the tryptic peptides detected in crude venom. Comparative evidence suggests that the neprilysin gene family is expressed in venoms across a range of spider taxa, but has undergone an expansion in the venoms of pholcids and may play a central functional role in these spiders. Bioassays of crude venoms on crickets resulted in an effective paralytic dose of 3.9 μg/g, which is comparable to that of crude venoms of Plectreurys tristis and other Synspermiata taxa. However, crickets exhibit flaccid paralysis and regions of darkening that are not observed after P. tristis envenomation. Documented bites on humans make clear that while these spiders can bite, the typical result is a mild sting with no long-lasting effects. Together, the evidence we present indicates pholcid venoms are a source of interesting new peptides and proteins, and effects of bites on humans and other mammals are inconsequential.
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- 2019
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26. Provider insight on surmounting specialty practice challenges to improve Tdap immunization rates among pregnant women
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Arpita Mehrotra, Allison Kennedy Fisher, Jennifer Mullen, Leslie Rodriguez, Angela J. Jiles, Alison P. Albert, Laura A. Randall, and Paula M. Frew
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Infectious disease ,Public health ,Medicine ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Background: Pertussis, or “whooping cough,” is an acute, contagious pulmonary disease that, despite being vaccine-preventable, has become an increasingly widespread problem in the United States. As a result, the Advisory Committee on Immunization Practices and American College of Obstetricians and Gynecologists updated recommendations stating clinicians should give a Tdap dose during every pregnancy, preferably at 27–36 weeks. Despite this recommendation, reported Tdap vaccine receipt rates during pregnancy vary from 16–61%, and previous studies have shown that clinician recommendation and vaccine administration are strongly associated with vaccine uptake among pregnant women. Methods: Our aim was to inform new strategies to increase uptake of the Tdap vaccine among pregnant women and, ultimately, reduce pertussis-related morbidity and mortality in infants. We conducted interviews with a sample of 24 ob-gyns. We subsequently performed grounded theory analyses of transcripts using deductive and inductive coding strategies followed by intercoder reliability assessment. Results: All physicians interviewed were familiar with the most recent recommendation of giving the Tdap vaccine during the third trimester of every pregnancy, and the majority of physicians stated that they felt that the vaccine was important and effective due to the transfer of pertussis antibodies from the mother to the fetus. Most physicians indicated that they recommended the vaccine to patients during pregnancy, but not all reported administering it on site because it was not stocked at their practice. Implementation challenges for physicians included insurance reimbursement and other challenges (i.e., patient refusal). Tdap vaccination during pregnancy was a lower clinical priority for some physicians. Physicians recognized the benefits associated with Tdap vaccination during pregnancy. Conclusions: Findings indicate while most ob-gyns recognize the benefits of Tdap and recommend vaccination during pregnancy, barriers such as insurance reimbursement and financial concerns for the practice can outweigh the perceived benefits. This resulted in some ob-gyns reporting choosing not to stock and administer the vaccine in their practice. Recommendations to address these concerns include 1) structural support for Tdap vaccine administration in ob-gyns practices; 2) Continuing medical education-equivalent educational interventions that address management techniques, vaccine coding, and other relevant information; and 3) interventions to assist physicians in communicating the importance of Tdap vaccination during pregnancy.
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- 2018
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27. Chorein Sensitive Arrangement of Cytoskeletal Architecture
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Sabina Honisch, Shuchen Gu, Jennifer Müller vom Hagen, Saad Alkahtani, Abdullah A. Al Kahtane, Anna Tsapara, Andreas Hermann, Alexander Storch, Ludger Schöls, Florian Lang, and Christos Stournaras
- Subjects
Desmin ,Cytokeratins ,Actin ,Tubulin ,Chorein ,Fibroblasts ,Physiology ,QP1-981 ,Biochemistry ,QD415-436 - Abstract
Background/Aims: Chorein is a protein expressed in various cell types. Loss of function mutations of the chorein encoding gene VPS13A lead to chorea-acanthocytosis, an autosomal recessive genetic disease characterized by movement disorder and behavioral abnormalities. Recent observations revealed that chorein is a powerful regulator of actin cytoskeleton in erythrocytes, platelets, K562 and endothelial HUVEC cells. Methods: In the present study we have used Western blotting to study actin polymerization dynamics, laser scanning microscopy to evaluate in detail the role of chorein in microfilaments, microtubules and intermediate filaments cytoskeleton architecture and RT-PCR to assess gene transcription of the cytoskeletal proteins. Results: We report here powerful depolymerization of actin microfilaments both, in erythrocytes and fibroblasts isolated from chorea-acanthocytosis patients. Along those lines, morphological analysis of fibroblasts from chorea-acanthocytosis patients showed disarranged microtubular network, when compared to fibroblasts from healthy donors. Similarly, the intermediate filament networks of desmin and cytokeratins showed significantly disordered organization with clearly diminished staining in patient's fibroblasts. In line with this, RT-PCR analysis revealed significant downregulation of desmin and cytokeratin gene transcripts. Conclusion: Our results provide for the first time evidence that defective chorein is accompanied by significant structural disorganization of all cytoskeletal structures in human fibroblasts from chorea-acanthocytosis patients.
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- 2015
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28. Correction to: Protocol for the Emory University African American Vaginal, oral, and gut microbiome in pregnancy cohort study
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Elizabeth J. Corwin, Carol J. Hogue, Bradley Pearce, Cherie C. Hill, Timothy D. Read, Jennifer Mulle, and Anne L. Dunlop
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Gynecology and obstetrics ,RG1-991 - Abstract
Abstract Following publication of the original article [1], the authors pointed out that the Methods included one step that is no longer necessary but which was inadvertently carried over from an earlier protocol.
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- 2017
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29. Infection and inflammation in schizophrenia and bipolar disorder: a genome wide study for interactions with genetic variation.
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Dimitrios Avramopoulos, Brad D Pearce, John McGrath, Paula Wolyniec, Ruihua Wang, Nicole Eckart, Alexandros Hatzimanolis, Fernando S Goes, Gerald Nestadt, Jennifer Mulle, Karen Coneely, Myfanwy Hopkins, Ingo Ruczinski, Robert Yolken, and Ann E Pulver
- Subjects
Medicine ,Science - Abstract
Inflammation and maternal or fetal infections have been suggested as risk factors for schizophrenia (SZ) and bipolar disorder (BP). It is likely that such environmental effects are contingent on genetic background. Here, in a genome-wide approach, we test the hypothesis that such exposures increase the risk for SZ and BP and that the increase is dependent on genetic variants. We use genome-wide genotype data, plasma IgG antibody measurements against Toxoplasma gondii, Herpes simplex virus type 1, Cytomegalovirus, Human Herpes Virus 6 and the food antigen gliadin as well as measurements of C-reactive protein (CRP), a peripheral marker of inflammation. The subjects are SZ cases, BP cases, parents of cases and screened controls. We look for higher levels of our immunity/infection variables and interactions between them and common genetic variation genome-wide. We find many of the antibody measurements higher in both disorders. While individual tests do not withstand correction for multiple comparisons, the number of nominally significant tests and the comparisons showing the expected direction are in significant excess (permutation p=0.019 and 0.004 respectively). We also find CRP levels highly elevated in SZ, BP and the mothers of BP cases, in agreement with existing literature, but possibly confounded by our inability to correct for smoking or body mass index. In our genome-wide interaction analysis no signal reached genome-wide significance, yet many plausible candidate genes emerged. In a hypothesis driven test, we found multiple interactions among SZ-associated SNPs in the HLA region on chromosome 6 and replicated an interaction between CMV infection and genotypes near the CTNNA3 gene reported by a recent GWAS. Our results support that inflammatory processes and infection may modify the risk for psychosis and suggest that the genotype at SZ-associated HLA loci modifies the effect of these variables on the risk to develop SZ.
- Published
- 2015
- Full Text
- View/download PDF
30. Are the Fenno-Scandinavian Arctic Wetlands a Significant Regional Source of Formic Acid?
- Author
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Benjamin T. Jones, Jennifer Muller, Sebastian O’Shea, Asan Bacak, Grant Allen, Martin Gallagher, Keith Bower, Michael Le Breton, Thomas J. Bannan, Stephane Bauguitte, John Pyle, Dave Lowry, Rebecca Fisher, James France, Euan Nisbet, Dudley Shallcross, and Carl Percival
- Subjects
formic acid ,CIMS ,aircraft measurements ,Arctic ,wetland ,soils ,Meteorology. Climatology ,QC851-999 - Abstract
This study presents the first gaseous formic acid (HC(O)OH) concentration measurements collected over the Fenno-Scandinavian wetlands (67.9–68.0° N, 22.1–27.8° E) as part of the MAMM (Methane and other greenhouse gases in the Arctic-Measurements, process studies and Modelling) aircraft campaigns conducted in August and September 2013. A boundary layer box model approach has been used to calculate a regionally representative (~240 km2) surface flux for HC(O)OH of 0.0098 (±0.0057) mg[HCOOH]·m−2·h−1. A surface-type classification map was used to estimate proportional source contributions to the observed HC(O)OH flux over the measurement region. The removal of expected source contributions (using available literature parameterisations) from the calculated surface flux identified that 75% remained unaccounted for. This may suggest that HC(O)OH emission from wetland within the Fenno-Scandinavian region could contribute up to 29 times higher per unit area than previous theoretical HC(O)OH globally-averaged wetland estimates, highlighting a need for further constrained wetland studies of HC(O)OH emission to better understand its potentially significant impact on the Arctic HC(O)OH budget and consequent impacts on oxidative capacity.
- Published
- 2017
- Full Text
- View/download PDF
31. A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci.
- Author
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Eimear E Kenny, Itsik Pe'er, Amir Karban, Laurie Ozelius, Adele A Mitchell, Sok Meng Ng, Monica Erazo, Harry Ostrer, Clara Abraham, Maria T Abreu, Gil Atzmon, Nir Barzilai, Steven R Brant, Susan Bressman, Edward R Burns, Yehuda Chowers, Lorraine N Clark, Ariel Darvasi, Dana Doheny, Richard H Duerr, Rami Eliakim, Nir Giladi, Peter K Gregersen, Hakon Hakonarson, Michelle R Jones, Karen Marder, Dermot P B McGovern, Jennifer Mulle, Avi Orr-Urtreger, Deborah D Proctor, Ann Pulver, Jerome I Rotter, Mark S Silverberg, Thomas Ullman, Stephen T Warren, Matti Waterman, Wei Zhang, Aviv Bergman, Lloyd Mayer, Seymour Katz, Robert J Desnick, Judy H Cho, and Inga Peter
- Subjects
Genetics ,QH426-470 - Abstract
Crohn's disease (CD) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD-susceptibility loci in individuals of European ancestry. An important epidemiological feature of CD is that it is 2-4 times more prevalent among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Europeans (NJ). To explore genetic variation associated with CD in AJs, we conducted a genome-wide association study (GWAS) by combining raw genotype data across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery stage, followed up by a replication study in 971 cases and 2,124 controls. We confirmed genome-wide significant associations of 9 known CD loci in AJs and replicated 3 additional loci with strong signal (p
- Published
- 2012
- Full Text
- View/download PDF
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