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Unconditional Cash Transfers For Reducing Poverty And Vulnerabilities: Effect On Use Of Health Services And Health Outcomes In Low-And Middle-Income Countries, Frank Pega, Sze Yan Liu, Stefan Walter, Roman Pabayo, Ruhi Saith, S L. Lhachimi Nov 2017

Unconditional Cash Transfers For Reducing Poverty And Vulnerabilities: Effect On Use Of Health Services And Health Outcomes In Low-And Middle-Income Countries, Frank Pega, Sze Yan Liu, Stefan Walter, Roman Pabayo, Ruhi Saith, S L. Lhachimi

Department of Public Health Scholarship and Creative Works

Background

Unconditional cash transfers (UCTs; provided without obligation) for reducing poverty and vulnerabilities (e.g. orphanhood, old age or HIV infection) are a type of social protection intervention that addresses a key social determinant of health (income) in low‐ and middle‐income countries (LMICs). The relative effectiveness of UCTs compared with conditional cash transfers (CCTs; provided so long as the recipient engages in prescribed behaviours such as using a health service or attending school) is unknown.

Objectives

To assess the effects of UCTs for improving health services use and health outcomes in vulnerable children and adults in LMICs. Secondary objectives are to …


Reducing Symptom Distress In Patients With Advanced Cancer Using An E-Alert System For Caregivers: Pooled Analysis Of Two Randomized Clinical Trials, David H. Gustafson, Lori L. Dubenske, Amy K. Atwood, Ming-Yuan Chih, Roberta A. Johnson, Fiona Mctavish, Andrew Quanbeck, Roger L. Brown, James F. Cleary, Dhavan Shah Nov 2017

Reducing Symptom Distress In Patients With Advanced Cancer Using An E-Alert System For Caregivers: Pooled Analysis Of Two Randomized Clinical Trials, David H. Gustafson, Lori L. Dubenske, Amy K. Atwood, Ming-Yuan Chih, Roberta A. Johnson, Fiona Mctavish, Andrew Quanbeck, Roger L. Brown, James F. Cleary, Dhavan Shah

Health and Clinical Sciences Faculty Publications

Background: Symptom distress in patients toward the end of life can change rapidly. Family caregivers have the potential to help patients manage those symptoms, as well as their own stress, if they are equipped with the proper resources. Electronic health (eHealth) systems may be able to provide those resources. Very sick patients may not be able to use such systems themselves to report their symptoms but family caregivers could.

Objective: The aim of this paper was to assess the effects on cancer patient symptom distress of an eHealth system that alerts clinicians to significant changes in the patient’s symptoms, as …


Cancer-Associated Fibroblasts Neutralize The Anti-Tumor Effect Of Csf1 Receptor Blockade By Inducing Pmn-Mdsc Infiltration Of Tumors., Vinit Kumar, Laxminarasimha Donthireddy, Douglas Marvel, Thomas Condamine, Fang Wang, Sergio Lavilla-Alonso, Ayumi Hashimoto, Prashanthi Vonteddu, Reeti Behera, Marlee A. Goins, Charles Mulligan, Brian Nam, Neil Hockstein, Fred Denstman, Shanti Shakamuri, David W. Speicher, Ashani T. Weeraratna, Timothy Chao, Robert H. Vonderheide, Lucia R. Languino, Peter Ordentlich, Qin Liu, Xiaowei Xu, Albert Lo, Ellen Puré, Chunsheng Zhang, Andrey Loboda, Manuel A. Sepulveda, Linda A. Snyder, Dmitry I. Gabrilovich Nov 2017

Cancer-Associated Fibroblasts Neutralize The Anti-Tumor Effect Of Csf1 Receptor Blockade By Inducing Pmn-Mdsc Infiltration Of Tumors., Vinit Kumar, Laxminarasimha Donthireddy, Douglas Marvel, Thomas Condamine, Fang Wang, Sergio Lavilla-Alonso, Ayumi Hashimoto, Prashanthi Vonteddu, Reeti Behera, Marlee A. Goins, Charles Mulligan, Brian Nam, Neil Hockstein, Fred Denstman, Shanti Shakamuri, David W. Speicher, Ashani T. Weeraratna, Timothy Chao, Robert H. Vonderheide, Lucia R. Languino, Peter Ordentlich, Qin Liu, Xiaowei Xu, Albert Lo, Ellen Puré, Chunsheng Zhang, Andrey Loboda, Manuel A. Sepulveda, Linda A. Snyder, Dmitry I. Gabrilovich

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Tumor-associated macrophages (TAM) contribute to all aspects of tumor progression. Use of CSF1R inhibitors to target TAM is therapeutically appealing, but has had very limited anti-tumor effects. Here, we have identified the mechanism that limited the effect of CSF1R targeted therapy. We demonstrated that carcinoma-associated fibroblasts (CAF) are major sources of chemokines that recruit granulocytes to tumors. CSF1 produced by tumor cells caused HDAC2-mediated downregulation of granulocyte-specific chemokine expression in CAF, which limited migration of these cells to tumors. Treatment with CSF1R inhibitors disrupted this crosstalk and triggered a profound increase in granulocyte recruitment to tumors. Combining CSF1R inhibitor with …


Cardiovascular Health Is Associated With Physical Function Among Older Community Dwelling Men And Women., Yichen Jin, Toshiko Tanaka, Yan Ma, Stefania Bandinelli, Luigi Ferrucci, Sameera A Talegawkar Nov 2017

Cardiovascular Health Is Associated With Physical Function Among Older Community Dwelling Men And Women., Yichen Jin, Toshiko Tanaka, Yan Ma, Stefania Bandinelli, Luigi Ferrucci, Sameera A Talegawkar

Exercise and Nutrition Sciences Faculty Publications

Background

Age related decline in physical function is a significant concern affecting the quality of life of older individuals.

Methods

We examined the associations between baseline overall cardiovascular health (CVH), its components, and physical function in 906 men and women from the InCHIANTI cohort. Physical function was assessed using the Short Performance Physical Battery and poor physical function was defined as an Short Performance Physical Battery score less than 10. Overall CVH score, ranging from 0 to 12 in the cohort, was operationalized using adherence to ideal levels for health behaviors including smoking status, physical activity, body mass index, and …


Comparison Of Inappropriate Shocks And Other Health Outcomes Between Single- And Dual-Chamber Implantable Cardioverter-Defibrillators For Primary Prevention Of Sudden Cardiac Death: Results From The Cardiovascular Research Network Longitudinal Study Of Implantable Cardioverter-Defibrillators, Pamela N. Peterson, Robert T. Greenlee, Alan S. Go, David J. Magid, Andrea E. Cassidy-Bushrow, Romel Garcia-Montilla, Karen A. Glenn, Jerry H. Gurwitz, Stephen C. Hammill, John Hayes, Alan Kadish, Kristi Reynolds, Param Sharma, David H. Smith, Paul D. Varosy, Humberto Vidaillet, Chan X. Zeng, Sharon-Lise T. Normand, Frederick A. Masoudi Nov 2017

Comparison Of Inappropriate Shocks And Other Health Outcomes Between Single- And Dual-Chamber Implantable Cardioverter-Defibrillators For Primary Prevention Of Sudden Cardiac Death: Results From The Cardiovascular Research Network Longitudinal Study Of Implantable Cardioverter-Defibrillators, Pamela N. Peterson, Robert T. Greenlee, Alan S. Go, David J. Magid, Andrea E. Cassidy-Bushrow, Romel Garcia-Montilla, Karen A. Glenn, Jerry H. Gurwitz, Stephen C. Hammill, John Hayes, Alan Kadish, Kristi Reynolds, Param Sharma, David H. Smith, Paul D. Varosy, Humberto Vidaillet, Chan X. Zeng, Sharon-Lise T. Normand, Frederick A. Masoudi

Public Health Sciences Articles

BACKGROUND: In US clinical practice, many patients who undergo placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death receive dual-chamber devices. The superiority of dual-chamber over single-chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single- and dual-chamber ICDs for primary prevention.

METHODS AND RESULTS: We identified patients receiving a single- or dual-chamber ICD for primary prevention who did not have an indication for pacing from 15 hospitals within 7 integrated health …


Precision Newborn Screening For Lysosomal Disorders, Melissa M. Minter Baerg, Stephanie D. Stoway, Jeremy Hart, Lea Mott, Dawn S. Peck, Stephanie L. Nett, Jason S. Eckerman, Jean M. Lacey, Coleman T. Turgeon, Dimitar Gavrilov, Devin Oglesbee, Kimiyo Raymond, Silvia Tortorelli, Dietrich Matern, Lars Mørkrid, Piero Rinaldo Nov 2017

Precision Newborn Screening For Lysosomal Disorders, Melissa M. Minter Baerg, Stephanie D. Stoway, Jeremy Hart, Lea Mott, Dawn S. Peck, Stephanie L. Nett, Jason S. Eckerman, Jean M. Lacey, Coleman T. Turgeon, Dimitar Gavrilov, Devin Oglesbee, Kimiyo Raymond, Silvia Tortorelli, Dietrich Matern, Lars Mørkrid, Piero Rinaldo

Pathology and Laboratory Medicine Faculty Publications

Purpose: The implementation of newborn screening for lysosomal disorders has uncovered overall poor specificity, psychosocial harm experienced by caregivers, and costly follow-up testing of false-positive cases. We report an informatics solution proven to minimize these issues.

Methods: The Kentucky Department for Public Health outsourced testing for mucopolysaccharidosis type I (MPS I) and Pompe disease, conditions recently added to the recommended uniform screening panel, plus Krabbe disease, which was added by legislative mandate. A total of 55,161 specimens were collected from infants born over 1 year starting from February 2016. Testing by tandem mass spectrometry was integrated with multivariate pattern recognition …


Tumor Suppressor Pdcd4 Attenuates Sin1 Translation To Inhibit Invasion In Colon Carcinoma, Qing Wang, Jiang Zhu, Ya-Wen Wang, Yong Dai, Yanlei Wang, Chi Wang, Jinpeng Liu, Alyson Baker, Nancy H. Colburn, Hsin-Sheng Yang Nov 2017

Tumor Suppressor Pdcd4 Attenuates Sin1 Translation To Inhibit Invasion In Colon Carcinoma, Qing Wang, Jiang Zhu, Ya-Wen Wang, Yong Dai, Yanlei Wang, Chi Wang, Jinpeng Liu, Alyson Baker, Nancy H. Colburn, Hsin-Sheng Yang

Toxicology and Cancer Biology Faculty Publications

Programmed cell death 4 (Pdcd4), a tumor invasion suppressor, is frequently downregulated in colorectal cancer and other cancers. In this study, we find that loss of Pdcd4 increases the activity of mammalian target of rapamycin complex 2 (mTORC2) and thereby upregulates Snail expression. Examining the components of mTORC2 showed that Pdcd4 knockdown increased the protein but not mRNA level of stress-activated-protein kinase interacting protein 1 (Sin1), which resulted from enhanced Sin1 translation. To understand how Pdcd4 regulates Sin1 translation, the SIN1 5′ untranslated region (5′UTR) was fused with luciferase reporter and named as 5′Sin1-Luc. Pdcd4 knockdown/knockout significantly increased the translation …


Epigenetic Etiology Of Intellectual Disability., Shigeki Iwase, Nathalie G Bérubé, Zhaolan Zhou, Nael Nadif Kasri, Elena Battaglioli, Marilyn Scandaglia, Angel Barco Nov 2017

Epigenetic Etiology Of Intellectual Disability., Shigeki Iwase, Nathalie G Bérubé, Zhaolan Zhou, Nael Nadif Kasri, Elena Battaglioli, Marilyn Scandaglia, Angel Barco

Paediatrics Publications

Intellectual disability (ID) is a prevailing neurodevelopmental condition associated with impaired cognitive and adaptive behaviors. Many chromatin-modifying enzymes and other epigenetic regulators have been genetically associated with ID disorders (IDDs). Here we review how alterations in the function of histone modifiers, chromatin remodelers, and methyl-DNA binding proteins contribute to neurodevelopmental defects and altered brain plasticity. We also discuss how progress in human genetics has led to the generation of mouse models that unveil the molecular etiology of ID, and outline the direction in which this field is moving to identify therapeutic strategies for IDDs. Importantly, because the chromatin regulators linked …


Low Arousal Positive Emotional Stimuli Attenuate Aberrant Working Memory Processing In Persons With Mild Cognitive Impairment, Lucas S. Broster, Shonna L. Jenkins, Sarah D. Holmes, Gregory A. Jicha, Yang Jiang Nov 2017

Low Arousal Positive Emotional Stimuli Attenuate Aberrant Working Memory Processing In Persons With Mild Cognitive Impairment, Lucas S. Broster, Shonna L. Jenkins, Sarah D. Holmes, Gregory A. Jicha, Yang Jiang

Behavioral Science Faculty Publications

Emotional enhancement effects on memory have been reported to mitigate the pathophysiology of Alzheimer’s disease (AD). However, relative to their manifestation in persons without pathologic aging, these effects may be reduced in magnitude or even deleterious, especially in tasks that more closely model ecologic memory performance. Based upon a synthesis of such reports, we hypothesized that in persons with AD low arousal positive stimuli would evoke relatively intact emotional enhancement effects, but that high arousal negative stimuli would evoke disordered emotional enhancement effects. To assess this, participants with and without mild cognitive impairment (MCI) presumed to be due to AD …


The Need For A Network To Establish And Validate Predictive Biomarkers In Cancer Immunotherapy., Giuseppe V Masucci, Alessandra Cesano, Alexander Eggermont, Bernard A Fox, Ena Wang, Francesco M Marincola, Gennaro Ciliberto, Kevin Dobbin, Igor Puzanov, Janis Taube, Jennifer Wargo, Lisa H Butterfield, Lisa Villabona, Magdalena Thurin, Michael A Postow, Paul M Sondel, Sandra Demaria, Sanjiv Agarwala, Paolo A Ascierto Nov 2017

The Need For A Network To Establish And Validate Predictive Biomarkers In Cancer Immunotherapy., Giuseppe V Masucci, Alessandra Cesano, Alexander Eggermont, Bernard A Fox, Ena Wang, Francesco M Marincola, Gennaro Ciliberto, Kevin Dobbin, Igor Puzanov, Janis Taube, Jennifer Wargo, Lisa H Butterfield, Lisa Villabona, Magdalena Thurin, Michael A Postow, Paul M Sondel, Sandra Demaria, Sanjiv Agarwala, Paolo A Ascierto

Articles, Abstracts, and Reports

Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, the entire medical oncology field has been revolutionized by the introduction of immune checkpoints inhibitors. Despite success in a variety of malignancies, responses typically only occur in a small percentage of patients for any given histology or treatment regimen. There are also concerns that immunotherapies are associated with immune-related toxicity as well as high costs. As such, identifying biomarkers to determine which patients are likely to derive clinical benefit from which immunotherapy and/or be susceptible to adverse side effects is a compelling clinical and …


Moonlighting Newborn Screening Markers: The Incidental Discovery Of A Second-Tier Test For Pompe Disease, Silvia Tortorelli, Jason S. Eckerman, Joseph J. Orsini, Colleen Stevens, Jeremy Hart, Patricia L. Hall, John J. Alexander, Dimitar Gavrilov, Devin Oglesbee, Kimiyo Raymond, Dietrich Matern, Piero Rinaldo Nov 2017

Moonlighting Newborn Screening Markers: The Incidental Discovery Of A Second-Tier Test For Pompe Disease, Silvia Tortorelli, Jason S. Eckerman, Joseph J. Orsini, Colleen Stevens, Jeremy Hart, Patricia L. Hall, John J. Alexander, Dimitar Gavrilov, Devin Oglesbee, Kimiyo Raymond, Dietrich Matern, Piero Rinaldo

Pathology and Laboratory Medicine Faculty Publications

Purpose: To describe a novel biochemical marker in dried blood spots suitable to improve the specificity of newborn screening for Pompe disease.

Methods: The new marker is a ratio calculated between the creatine/creatinine (Cre/Crn) ratio as the numerator and the activity of acid α-glucosidase (GAA) as the denominator. Using Collaborative Laboratory Integrated Reports (CLIR), the new marker was incorporated in a dual scatter plot that can achieve almost complete segregation between Pompe disease and false-positive cases.

Results: The (Cre/Crn)/GAA ratio was measured in residual dried blood spots of five Pompe cases and was found to be elevated (range 4.41–13.26; 99%ile …


Tumor And Microenvironment Evolution During Immunotherapy With Nivolumab., Nadeem Riaz, Jonathan J Havel, Vladimir Makarov, Alexis Desrichard, Walter Urba, Jennifer S Sims, F Stephen Hodi, Salvador Martín-Algarra, Rajarsi Mandal, William H Sharfman, Shailender Bhatia, Wen-Jen Hwu, Thomas F Gajewski, Craig L Slingluff, Diego Chowell, Sviatoslav M Kendall, Han Chang, Rachna Shah, Fengshen Kuo, Luc G T Morris, John-William Sidhom, Jonathan P Schneck, Christine E Horak, Nils Weinhold, Timothy A Chan Nov 2017

Tumor And Microenvironment Evolution During Immunotherapy With Nivolumab., Nadeem Riaz, Jonathan J Havel, Vladimir Makarov, Alexis Desrichard, Walter Urba, Jennifer S Sims, F Stephen Hodi, Salvador Martín-Algarra, Rajarsi Mandal, William H Sharfman, Shailender Bhatia, Wen-Jen Hwu, Thomas F Gajewski, Craig L Slingluff, Diego Chowell, Sviatoslav M Kendall, Han Chang, Rachna Shah, Fengshen Kuo, Luc G T Morris, John-William Sidhom, Jonathan P Schneck, Christine E Horak, Nils Weinhold, Timothy A Chan

Articles, Abstracts, and Reports

The mechanisms by which immune checkpoint blockade modulates tumor evolution during therapy are unclear. We assessed genomic changes in tumors from 68 patients with advanced melanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after nivolumab initiation (CA209-038 study). Tumors were analyzed by whole-exome, transcriptome, and/or T cell receptor (TCR) sequencing. In responding patients, mutation and neoantigen load were reduced from baseline, and analysis of intratumoral heterogeneity during therapy demonstrated differential clonal evolution within tumors and putative selection against neoantigenic mutations on-therapy. Transcriptome analyses before and during nivolumab therapy revealed increases in distinct immune cell subsets, activation of specific …


Differential Impact Of Serial Measurement Of Nonplatelet Thromboxane Generation On Long-Term Outcome After Cardiac Surgery., Nikolaos Kakouros, Tyler J Gluckman, John V Conte, Thomas S Kickler, Katherine Laws, Bruce A Barton, Jeffrey J Rade Nov 2017

Differential Impact Of Serial Measurement Of Nonplatelet Thromboxane Generation On Long-Term Outcome After Cardiac Surgery., Nikolaos Kakouros, Tyler J Gluckman, John V Conte, Thomas S Kickler, Katherine Laws, Bruce A Barton, Jeffrey J Rade

Articles, Abstracts, and Reports

BACKGROUND: Systemic thromboxane generation, not suppressible by standard aspirin therapy and likely arising from nonplatelet sources, increases the risk of atherothrombosis and death in patients with cardiovascular disease. In the RIGOR (Reduction in Graft Occlusion Rates) study, greater nonplatelet thromboxane generation occurred early compared with late after coronary artery bypass graft surgery, although only the latter correlated with graft failure. We hypothesize that a similar differential association exists between nonplatelet thromboxane generation and long-term clinical outcome.

METHODS AND RESULTS: Five-year outcome data were analyzed for 290 RIGOR subjects taking aspirin with suppressed platelet thromboxane generation. Multivariable modeling was performed to …


Hypotonia And Intellectual Disability Without Dysmorphic Features In A Patient With Pign-Related Disease., Isabelle Thiffault, Britton Zuccarelli, Holly Welsh, Xuan Yuan, Emily Farrow, Lee Zellmer, Neil Miller, Sarah Soden, Ahmed Abdelmoity, Robert A Brodsky, Carol Saunders Nov 2017

Hypotonia And Intellectual Disability Without Dysmorphic Features In A Patient With Pign-Related Disease., Isabelle Thiffault, Britton Zuccarelli, Holly Welsh, Xuan Yuan, Emily Farrow, Lee Zellmer, Neil Miller, Sarah Soden, Ahmed Abdelmoity, Robert A Brodsky, Carol Saunders

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Defects in the human glycosylphosphatidylinositol anchor biosynthetic pathway are associated with inherited glycosylphosphatidylinositol (GPI)-deficiencies characterized by a broad range of clinical phenotypes including multiple congenital anomalies, dysmorphic faces, developmental delay, hypotonia, and epilepsy. Biallelic variants in PIGN, encoding phosphatidylinositol-glycan biosynthesis class N have been recently associated with multiple congenital anomalies hypotonia seizure syndrome.

CASE PRESENTATION: Our patient is a 2 year old male with hypotonia, global developmental delay, and focal epilepsy. Trio whole-exome sequencing revealed heterozygous variants in PIGN, c.181G > T (p.Glu61*) and c.284G > A (p.Arg95Gln). Analysis of FLAER and anti-CD59 by flow-cytometry demonstrated a shift in this patient's …


B Cell-Derived Il-4 Acts On Podocytes To Induce Proteinuria And Foot Process Effacement, Alfred Hj Kim, Jun-Jae Chung, Shreeram Akilesh, Ania Koziell, Sanjay Jain, Jeffrey B. Hodgin, Mark J. Miller, Thaddeus S. Stappenbeck, Jeffrey H. Miner, Andrey S. Shaw Nov 2017

B Cell-Derived Il-4 Acts On Podocytes To Induce Proteinuria And Foot Process Effacement, Alfred Hj Kim, Jun-Jae Chung, Shreeram Akilesh, Ania Koziell, Sanjay Jain, Jeffrey B. Hodgin, Mark J. Miller, Thaddeus S. Stappenbeck, Jeffrey H. Miner, Andrey S. Shaw

Open Access Publications

The efficacy of B cell depletion therapies in diseases such as nephrotic syndrome and rheumatoid arthritis suggests a broader role in B cells in human disease than previously recognized. In some of these diseases, such as the minimal change disease subtype of nephrotic syndrome, pathogenic antibodies and immune complexes are not involved. We hypothesized that B cells, activated in the kidney, might produce cytokines capable of directly inducing cell injury and proteinuria. To directly test our hypothesis, we targeted a model antigen to the kidney glomerulus and showed that transfer of antigen-specific B cells could induce glomerular injury and proteinuria. …


Identification Of A Novel Synaptic Protein, Tmtc3, Involved In Periventricular Nodular Heterotopia With Intellectual Disability And Epilepsy, Sali M K Farhan, Kevin C J Nixon, Michelle Everest, Tara N Edwards, Shirley Long, Dmitri Segal, Maria J Knip, Heleen H Arts, Rana Chakrabarti, Jian Wang, John F Robinson, Donald Lee, Seyed M Mirsattari, C Anthony Rupar, Victoria M Siu, Forge Canada Consortium, Michael O Poulter, Robert A Hegele, Jamie M Kramer Nov 2017

Identification Of A Novel Synaptic Protein, Tmtc3, Involved In Periventricular Nodular Heterotopia With Intellectual Disability And Epilepsy, Sali M K Farhan, Kevin C J Nixon, Michelle Everest, Tara N Edwards, Shirley Long, Dmitri Segal, Maria J Knip, Heleen H Arts, Rana Chakrabarti, Jian Wang, John F Robinson, Donald Lee, Seyed M Mirsattari, C Anthony Rupar, Victoria M Siu, Forge Canada Consortium, Michael O Poulter, Robert A Hegele, Jamie M Kramer

Paediatrics Publications

Defects in neuronal migration cause brain malformations, which are associated with intellectual disability (ID) and epilepsy. Using exome sequencing, we identified compound heterozygous variants (p.Arg71His and p. Leu729ThrfsTer6) in TMTC3, encoding transmembrane and tetratricopeptide repeat containing 3, in four siblings with nocturnal seizures and ID. Three of the four siblings have periventricular nodular heterotopia (PVNH), a common brain malformation caused by failure of neurons to migrate from the ventricular zone to the cortex. Expression analysis using patient-derived cells confirmed reduced TMTC3 transcript levels and loss of the TMTC3 protein compared to parental and control cells. As TMTC3 function is currently …


Canadian Guidelines For Controlled Pediatric Donation After Circulatory Determination Of Death-Summary Report, Matthew J Weiss, Laura Hornby, Bram Rochwerg, Michael Van Manen, Sonny Dhanani, V Ben Sivarajan, Amber Appleby, Mary Bennett, Daniel Buchman, Catherine Farrell, Aviva Goldberg, Rebecca Greenberg, Ram Singh, Thomas A Nakagawa, William Witteman, Jill Barter, Allon Beck, Kevin Coughlin, Alf Conradi, Cynthia Cupido, Rosanne Dawson, Anne Dipchand, Darren Freed, Karen Hornby, Valerie Langlois, Cheryl Mack, Meagan Mahoney, Deepak Manhas, Christopher Tomlinson, Samara Zavalkoff, Sam D Shemie Nov 2017

Canadian Guidelines For Controlled Pediatric Donation After Circulatory Determination Of Death-Summary Report, Matthew J Weiss, Laura Hornby, Bram Rochwerg, Michael Van Manen, Sonny Dhanani, V Ben Sivarajan, Amber Appleby, Mary Bennett, Daniel Buchman, Catherine Farrell, Aviva Goldberg, Rebecca Greenberg, Ram Singh, Thomas A Nakagawa, William Witteman, Jill Barter, Allon Beck, Kevin Coughlin, Alf Conradi, Cynthia Cupido, Rosanne Dawson, Anne Dipchand, Darren Freed, Karen Hornby, Valerie Langlois, Cheryl Mack, Meagan Mahoney, Deepak Manhas, Christopher Tomlinson, Samara Zavalkoff, Sam D Shemie

Paediatrics Publications

OBJECTIVES: Create trustworthy, rigorous, national clinical practice guidelines for the practice of pediatric donation after circulatory determination of death in Canada.

METHODS: We followed a process of clinical practice guideline development based on World Health Organization and Canadian Medical Association methods. This included application of Grading of Recommendations Assessment, Development, and Evaluation methodology. Questions requiring recommendations were generated based on 1) 2006 Canadian donation after circulatory determination of death guidelines (not pediatric specific), 2) a multidisciplinary symposium of national and international pediatric donation after circulatory determination of death leaders, and 3) a scoping review of the pediatric donation after circulatory …


Disparities In Rate, Triggers, And Management In Pediatric And Adult Cases Of Suspected Drug-Induced Anaphylaxis In Canada, Sofianne Gabrielli, Ann E Clarke, Harley Eisman, Judy Morris, Lawrence Joseph, Sebastien La Vieille, Peter Small, Rodrick Lim, Paul Enarson, Michal Zelcer, Edmond S Chan, Chris Mill, Moshe Ben-Shoshan Nov 2017

Disparities In Rate, Triggers, And Management In Pediatric And Adult Cases Of Suspected Drug-Induced Anaphylaxis In Canada, Sofianne Gabrielli, Ann E Clarke, Harley Eisman, Judy Morris, Lawrence Joseph, Sebastien La Vieille, Peter Small, Rodrick Lim, Paul Enarson, Michal Zelcer, Edmond S Chan, Chris Mill, Moshe Ben-Shoshan

Paediatrics Publications

Introduction

Data is sparse on drug-induced anaphylaxis (DIA) and there have not been studies assessing the differences in clinical characteristics and management of DIA between adults and children.

Objective

We assessed the percentage, diagnosis, and management of DIA among all anaphylaxis visits in three pediatric and one adult emergency departments (ED) across Canada.

Methods

Children presenting to the Montreal Children's Hospital (MCH), British Columbia Children's Hospital (BCCH), and Children's Hospital at London Health Sciences Center and adults presenting to Hôpital du Sacré-Coeur with anaphylaxis were recruited as part of the Cross-Canada Anaphylaxis Registry. A standardized data form documenting the reaction …


Suppurative Complications Of Acute Hematogenous Osteomyelitis In Children, Jennifer J. Johnston, Cristina Murray-Krezan, Walter N. Dehority Nov 2017

Suppurative Complications Of Acute Hematogenous Osteomyelitis In Children, Jennifer J. Johnston, Cristina Murray-Krezan, Walter N. Dehority

Pediatrics Research and Scholarship

We carried out a case-control study in children with acute hematogenous osteomyelitis (AHO) with and without suppurative complications discharged from our institution over an 11-year period to test the hypothesis that abscess formation was associated with a delayed presentation to care. Of 102 children with AHO, 54 abscesses were documented in 46 patients (25 bone, 29 muscle). A delay in presentation was not associated with abscess formation (6.5 vs. 5.0 days, P=0.26). Overall, 78% of all bone abscesses were visible on initial MRI. Consistent use of MRI at presentation may identify children with suppurative complications of AHO.


Efficacy And Safety Of Pembrolizumab In Patients Enrolled In Keynote-030 In The United States: An Expanded Access Program., Tara C Gangadhar, Wen-Jen Hwu, Michael A Postow, Omid Hamid, Adil Daud, Roxana Dronca, Richard Joseph, Steven J O'Day, F S Hodi, Anna C Pavlick, Harriet Kluger, Romina P Oxborough, Aiming Yang, Mihaela Gazdoiu, Debra A Kush, Scot Ebbinghaus, April K S Salama Nov 2017

Efficacy And Safety Of Pembrolizumab In Patients Enrolled In Keynote-030 In The United States: An Expanded Access Program., Tara C Gangadhar, Wen-Jen Hwu, Michael A Postow, Omid Hamid, Adil Daud, Roxana Dronca, Richard Joseph, Steven J O'Day, F S Hodi, Anna C Pavlick, Harriet Kluger, Romina P Oxborough, Aiming Yang, Mihaela Gazdoiu, Debra A Kush, Scot Ebbinghaus, April K S Salama

Articles, Abstracts, and Reports

KEYNOTE-030 (ClinicalTrials.gov ID, NCT02083484) was a global expanded access program that allowed access to pembrolizumab, an antiprogrammed death 1 antibody, for patients with advanced melanoma before its regulatory approval. Patients with unresectable stage III/IV melanoma that progressed after standard-of-care therapy, including ipilimumab and, if BRAF mutant, a BRAF inhibitor, were eligible to receive pembrolizumab 2 mg/kg every 3 weeks. Response was assessed by immune-related response criteria by investigator review. Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. In the United States, 979 patients enrolled between April and September 2014. …


Tox Regulates Growth, Dna Repair, And Genomic Instability In T-Cell Acute Lymphoblastic Leukemia, Riadh Lobbardi, Jordan Pinder, Barbara Martinez-Pastor, Marina Theodorou, Jessica S. Blackburn, Brian J. Abraham, Yuka Namiki, Marc Mansour, Nouran S. Abdelfattah, Aleksey Molodtsov, Gabriela Alexe, Debra Toiber, Manon De Waard, Esha Jain, Myriam Boukhali, Mattia Lion, Deepak Bhere, Khalid Shah, Alejandro Gutierrez, Kimberly Stegmaier, Lewis B. Silverman, Ruslan I. Sadreyev, John M. Asara, Marjorie A. Oettinger, Wilhelm Haas, A. Thomas Look, Richard A. Young, Raul Mostoslavsky, Graham Dellaire, David M. Langenau Nov 2017

Tox Regulates Growth, Dna Repair, And Genomic Instability In T-Cell Acute Lymphoblastic Leukemia, Riadh Lobbardi, Jordan Pinder, Barbara Martinez-Pastor, Marina Theodorou, Jessica S. Blackburn, Brian J. Abraham, Yuka Namiki, Marc Mansour, Nouran S. Abdelfattah, Aleksey Molodtsov, Gabriela Alexe, Debra Toiber, Manon De Waard, Esha Jain, Myriam Boukhali, Mattia Lion, Deepak Bhere, Khalid Shah, Alejandro Gutierrez, Kimberly Stegmaier, Lewis B. Silverman, Ruslan I. Sadreyev, John M. Asara, Marjorie A. Oettinger, Wilhelm Haas, A. Thomas Look, Richard A. Young, Raul Mostoslavsky, Graham Dellaire, David M. Langenau

Molecular and Cellular Biochemistry Faculty Publications

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes. Using a transgenic screen in zebrafish, thymocyte selection–associated high mobility group box protein (TOX) was uncovered as a collaborating oncogenic driver that accelerated T-ALL onset by expanding the initiating pool of transformed clones and elevating genomic instability. TOX is highly expressed in a majority of human T-ALL and is required for proliferation and continued xenograft growth in mice. Using a wide array of functional analyses, we uncovered that TOX binds directly to KU70/80 and suppresses recruitment of this complex to DNA breaks to inhibit nonhomologous end joining (NHEJ) repair. …


Learning From Kids, Alicia Neu, Jerry Yee Nov 2017

Learning From Kids, Alicia Neu, Jerry Yee

Nephrology Articles

No abstract provided.


Ordinal Convolutional Neural Networks For Predicting Rdoc Positive Valence Psychiatric Symptom Severity Scores, Anthony Rios, Ramakanth Kavuluru Nov 2017

Ordinal Convolutional Neural Networks For Predicting Rdoc Positive Valence Psychiatric Symptom Severity Scores, Anthony Rios, Ramakanth Kavuluru

Computer Science Faculty Publications

Background—The CEGS N-GRID 2016 Shared Task in Clinical Natural Language Processing (NLP) provided a set of 1000 neuropsychiatric notes to participants as part of a competition to predict psychiatric symptom severity scores. This paper summarizes our methods, results, and experiences based on our participation in the second track of the shared task.

Objective—Classical methods of text classification usually fall into one of three problem types: binary, multi-class, and multi-label classification. In this effort, we study ordinal regression problems with text data where misclassifications are penalized differently based on how far apart the ground truth and model predictions are …


Predicting Mental Conditions Based On "History Of Present Illness" In Psychiatric Notes With Deep Neural Networks, Tung Tran, Ramakanth Kavuluru Nov 2017

Predicting Mental Conditions Based On "History Of Present Illness" In Psychiatric Notes With Deep Neural Networks, Tung Tran, Ramakanth Kavuluru

Computer Science Faculty Publications

Background—Applications of natural language processing to mental health notes are not common given the sensitive nature of the associated narratives. The CEGS N-GRID 2016 Shared Task in Clinical Natural Language Processing (NLP) changed this scenario by providing the first set of neuropsychiatric notes to participants. This study summarizes our efforts and results in proposing a novel data use case for this dataset as part of the third track in this shared task.

Objective—We explore the feasibility and effectiveness of predicting a set of common mental conditions a patient has based on the short textual description of patient’s history …


Predictors Of Sleepiness In Obstructive Sleep Apnoea At Baseline And After 6 Months Of Continuous Positive Airway Pressure Therapy., Rohit Budhiraja, Clete A Kushida, Deborah A Nichols, James K Walsh, Richard D Simon, Daniel J Gottlieb, Stuart F Quan Nov 2017

Predictors Of Sleepiness In Obstructive Sleep Apnoea At Baseline And After 6 Months Of Continuous Positive Airway Pressure Therapy., Rohit Budhiraja, Clete A Kushida, Deborah A Nichols, James K Walsh, Richard D Simon, Daniel J Gottlieb, Stuart F Quan

Articles, Abstracts, and Reports

We evaluated factors associated with subjective and objective sleepiness at baseline and after 6 months of continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnoea (OSA).We analysed data from the Apnoea Positive Pressure Long-term Efficacy Study (APPLES), a prospective 6-month multicentre randomised controlled trial with 1105 subjects with OSA, 558 of who were randomised to active CPAP. Epworth sleepiness scale (ESS) scores and the mean sleep latency (MSL) on the maintenance of wakefulness test at baseline and after 6 months of CPAP therapy were recorded.Excessive sleepiness (ESS score >10) was present in 543 (49.1%) participants. Younger age, …


Second Primary Malignant Neoplasms And Survival In Adolescent And Young Adult Cancer Survivors., Theresa H M Keegan, Archie Bleyer, Aaron S Rosenberg, Qian Li, Melanie Goldfarb Nov 2017

Second Primary Malignant Neoplasms And Survival In Adolescent And Young Adult Cancer Survivors., Theresa H M Keegan, Archie Bleyer, Aaron S Rosenberg, Qian Li, Melanie Goldfarb

Articles, Abstracts, and Reports

Importance: Although the increased incidence of second primary malignant neoplasms (SPMs) is a well-known late effect after cancer, few studies have compared survival after an SPM to survival of the same cancer occurring as first primary malignant neoplasm (PM) by age.

Objective: To assess the survival impact of SPMs in adolescents and young adults (AYAs) (15-39 years) compared with that of pediatric (<15 >years) and older adult (≥40 years) patients with the same SPMs.

Design, Setting, and Participants: This was a population-based, retrospective cohort study of patients with cancer in 13 Surveillance, Epidemiology and End Results regions in the United …


Characteristics Associated With Requests By Pathologists For Second Opinions On Breast Biopsies., Berta M Geller, Heidi D Nelson, Donald L Weaver, Paul D Frederick, Kimberly H Allison, Tracy Onega, Patricia A Carney, Anna N A Tosteson, Joann G Elmore Nov 2017

Characteristics Associated With Requests By Pathologists For Second Opinions On Breast Biopsies., Berta M Geller, Heidi D Nelson, Donald L Weaver, Paul D Frederick, Kimberly H Allison, Tracy Onega, Patricia A Carney, Anna N A Tosteson, Joann G Elmore

Articles, Abstracts, and Reports

AIMS: Second opinions in pathology improve patient safety by reducing diagnostic errors, leading to more appropriate clinical treatment decisions. Little objective data are available regarding the factors triggering a request for second opinion despite second opinion consultations being part of the diagnostic system of pathology. Therefore we sought to assess breast biopsy cases and interpreting pathologists characteristics associated with second opinion requests.

METHODS: Collected pathologist surveys and their interpretations of 60 test set cases were used to explore the relationships between case characteristics, pathologist characteristics and case perceptions, and requests for second opinions. Data were evaluated by logistic regression and …


Rapid Rest/Stress Regadenoson Ungated Perfusion Cmr For Detection Of Coronary Artery Disease In Patients With Atrial Fibrillation., Erik T Bieging, I Haider, G Adluru, L Chang, P Suksaranjit, D Likhite, A Shaaban, L Jensen, B D Wilson, C J Mcgann, E Dibella Nov 2017

Rapid Rest/Stress Regadenoson Ungated Perfusion Cmr For Detection Of Coronary Artery Disease In Patients With Atrial Fibrillation., Erik T Bieging, I Haider, G Adluru, L Chang, P Suksaranjit, D Likhite, A Shaaban, L Jensen, B D Wilson, C J Mcgann, E Dibella

Articles, Abstracts, and Reports

Cardiovascular magnetic resonance (CMR) perfusion has been established as a useful imaging modality for the detection of coronary artery disease (CAD). However, there are several limitations when applying standard, ECG-gated stress/rest perfusion CMR to patients with atrial fibrillation (AF). In this study we investigate an approach with no ECG gating and a rapid rest/stress perfusion protocol to determine its accuracy for detection of CAD in patients with AF. 26 patients with AF underwent a rapid rest/regadenoson stress CMR perfusion imaging protocol, and all patients had X-ray coronary angiography. An ungated radial myocardial perfusion sequence was used. Imaging protocol included: rest …


Organic Solvent Exposure And Depressive Symptoms Among Licensed Pesticide Applicators In The Agricultural Health Study, Miriam Siegel, Sarah E. Starks, Wayne T. Sanderson, Freya Kamel, Jane A. Hoppin, Fred Gerr Nov 2017

Organic Solvent Exposure And Depressive Symptoms Among Licensed Pesticide Applicators In The Agricultural Health Study, Miriam Siegel, Sarah E. Starks, Wayne T. Sanderson, Freya Kamel, Jane A. Hoppin, Fred Gerr

Epidemiology and Environmental Health Faculty Publications

Purpose

Although organic solvents are often used in agricultural operations, neurotoxic effects of solvent exposure have not been extensively studied among farmers. The current analysis examined associations between questionnaire-based metrics of organic solvent exposure and depressive symptoms among farmers.

Methods

Results from 692 male Agricultural Health Study participants were analyzed. Solvent type and exposure duration were assessed by questionnaire. An “ever-use” variable and years of use categories were constructed for exposure to gasoline, paint/lacquer thinner, petroleum distillates, and any solvent. Depressive symptoms were ascertained with the Center for Epidemiologic Studies Depression Scale (CES-D); scores were analyzed separately as continuous (0–60) …


A Rural/Urban Comparison Of Privacy And Confidentiality Concerns Associated With Providing Sensitive Location Information In Epidemiologic Research Involving Persons Who Use Drugs, Abby E. Rudolph, April M. Young, Jennifer R. Havens Nov 2017

A Rural/Urban Comparison Of Privacy And Confidentiality Concerns Associated With Providing Sensitive Location Information In Epidemiologic Research Involving Persons Who Use Drugs, Abby E. Rudolph, April M. Young, Jennifer R. Havens

Epidemiology and Environmental Health Faculty Publications

Background—Analyses that link contextual factors with individual-level data can improve our understanding of the "risk environment"; however, the accuracy of information provided by participants about locations where illegal/stigmatized behaviors occur may be influenced by privacy/confidentiality concerns that may vary by setting and/or data collection approach.

Methods—We recruited thirty-five persons who use drugs from a rural Appalachian town and a Mid-Atlantic city to participate in in-depth interviews. Through thematic analyses, we identified and compared privacy/confidentiality concerns associated with two survey methods that (1) collect self-reported addresses/cross-streets and (2) use an interactive web-based map to find/confirm locations in rural and …