Medical Sciences Commons^™

Integrative Genomic And Transcriptomic Analysis For Pinpointing Recurrent Alterations Of Plant Homeodomain Genes And Their Clinical Significance In Breast Cancer, Huimei Yu, Yuanyuan Jiang, Lanxin Liu, Wenqi Shan, Xiaofang Chu, Zhe Yang, Zeng-Quan Yang

Oncology Faculty Publications

A wide range of the epigenetic effectors that regulate chromatin modification, gene expression, genomic stability, and DNA repair contain structurally conserved domains called plant homeodomain (PHD) fingers. Alternations of several PHD finger-containing proteins (PHFs) due to genomic amplification, mutations, deletions, and translocations have been linked directly to various types of cancer. However, little is known about the genomic landscape and the clinical significance of PHFs in breast cancer. Hence, we performed a large-scale genomic and transcriptomic analysis of 98 PHF genes in breast cancer using TCGA and METABRIC datasets and correlated the recurrent alterations with clinicopathological features and survival of …

Immunogenicity And Protective Efficacy Of The Dar-901 Booster Vaccine In A Murine Model Of Tuberculosis, Timothy Lahey, Dominick Laddy, Krystal Hill, Jacqueline Schaeffer

Dartmouth Scholarship

The development of a novel tuberculosis vaccine is a leading global health priority. SRL172, an inactivated, whole-cell mycobacterial vaccine, was safe, immunogenic and reduced the incidence of culture-confirmed tuberculosis in a phase III trial in HIV-infected and BCG immunized adults in Tanzania. Here we describe the immunogenicity and protective efficacy of DAR-901, a booster vaccine against tuberculosis manufactured from the same seed strain using a new scalable method.

Motility And Adhesion Through Type Iv Pili In Gram-Positive Bacteria, Kurt H. Piepenbrink, Eric J. Sundberg

Food for Health: Publications

Type IV pili are hair-like bacterial surface appendages that play a role in diverse processes such as cellular adhesion, colonization, twitching motility, biofilm formation, and horizontal gene transfer. These extracellular fibers are composed exclusively or primarily of many copies of one or more pilin proteins, tightly packed in a helix so that the highly hydrophobic amino-terminus of the pilin is buried in the pilus core. Type IV pili have been characterized extensively in Gram-negative bacteria, and recent advances in high-throughput genomic sequencing have revealed that they are also widespread in Gram-positive bacteria. Here, we review the current state of knowledge …

Mobilising Expertise And Resources To Close The Radiotherapy Gap In Cancer Care., D Rodin, J Longo, T Sherertz, M M Shah, O Balagun, N Wendling, Jacob Van Dyk, C N Coleman, M J Xu, S Grover

Oncology Publications

Closing the gap in cancer care within low- and middle-income countries and in indigenous and geographically isolated populations in high-income countries requires investment and innovation. This is particularly true for radiotherapy, for which the global disparity is one of the largest in healthcare today. New models and paradigms and non-traditional collaborations have been proposed to improve global equity in cancer control. We describe recent initiatives from within the radiation oncology community to increase access to treatment, build the low- and middle-income countries' radiation oncology workforce, mobilise more professionals from within high-income countries and raise awareness of the global need for …

Analysis Of Global Radiotherapy Needs And Costs By Geographic Region And Income Level., E Zubizarreta, Jacob Van Dyk, Y Lievens

Oncology Publications

Recent years have seen various reviews on the lack of access to radiotherapy often based on geographic regions of the world such as Africa, Asia Pacific, Europe, Latin America and North America. Countries are often defined by their national income per capita levels based on World Bank definitions of high income, upper middle income, lower middle income and low income. Within the world regions, there are significant variations in gross national income (GNI) per capita among the different countries, and even within similar income levels, large variations exist. This report presents the actual status of radiotherapy and analyses the current …

Applying Multiple Data Collection Tools To Quantify Human Papillomavirus Vaccine Communication On Twitter., Philip M. Massey, Amy Leader, Elad Yom-Tov, Alexandra Budenz, Kara Fisher, Ann C. Klassen

Department of Medical Oncology Faculty Papers

BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. There are several vaccines that protect against strains of HPV most associated with cervical and other cancers. Thus, HPV vaccination has become an important component of adolescent preventive health care. As media evolves, more information about HPV vaccination is shifting to social media platforms such as Twitter. Health information consumed on social media may be especially influential for segments of society such as younger populations, as well as ethnic and racial minorities.

OBJECTIVE: The objectives of our study were to quantify HPV vaccine communication on …

Self-Reported Sleep Apnea And Dementia Risk: Findings From The Prevention Of Alzheimer's Disease With Vitamin E And Selenium Trial, Xiuhua Ding, Richard J. Kryscio, Joshua Turner, Gregory A. Jicha, Gregory E. Cooper, Allison M. Caban-Holt, Frederick A. Schmitt, Erin L. Abner

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVES: To investigate the association between baseline sleep apnea and risk of incident dementia in the Prevention of Alzheimer's Disease with Vitamin E and Selenium (PREADViSE) study and to explore whether the association depends on apolipoprotein E (APOE) ɛ4 allele status.

DESIGN: Secondary analysis based on data collected during PREADViSE.

SETTING: Participants were assessed at 128 local clinical study sites during the clinical trial phase and later were followed by telephone from a centralized location.

PARTICIPANTS: Men enrolled in PREADViSE (without dementia or other active neurological conditions that affect cognition such as major psychiatric disorders, including depression; N = …

Post-Concussion Experiences Of Collegiate Student-Athletes, Kaitlin Iris Singer

Doctoral Dissertations

Sports-related concussions are a major public health concern affecting a significant number of collegiate student-athletes. Medical and public health research has addressed every aspect of concussion management processes including concussion education, medical diagnosis, recovery, and returning to sport and classroom. This research has led to several best-practices for concussion management. Since 2010, the NCAA has mandated that its member institutions maintain concussion management policies and procedures. However, the current recommendations, based primarily on medical research, have been found in quantitative studies of the behaviors and practices of athletic trainers, coaches, and student-athletes to be ineffective. To date, no studies have …

Multipoint Genome-Wide Linkage Scan For Nonword Repetition In A Multigenerational Family Further Supports Chromosome 13q As A Locus For Verbal Trait Disorders, D. T. Truong, L. D. Shriberg, S. D. Smith, K. L. Chapman, A. R. Scheer-Cohen, M. M.C. Demille, A. K. Adams, Alejandro Q. Nato Jr., E. M. Wijsman, J. D. Eicher, J. R. Gruen

Biochemistry and Microbiology

Verbal trait disorders encompass a wide range of conditions and are marked by deficits in five domains that impair a person’s ability to communicate: speech, language, reading, spelling, and writing. Nonword repetition is a robust endophenotype for verbal trait disorders that is sensitive to cognitive processes critical to verbal development, including auditory processing, phonological working memory, and motor planning and programming. In the present study, we present a six-generation extended pedigree with a history of verbal trait disorders. Using genome-wide multipoint variance component linkage analysis of nonword repetition, we identified a region spanning chromosome 13q14–q21 with LOD = 4.45 between …

Baylisascaris Procyonis Exposure Case Study, Andrea M. Lauffer M.D., Patricia Lutz M.D., Susan L. Flesher M.D.

Pediatrics

We report a case of exposure to raccoon feces found to be contaminated with baylisascaris procyonis. The exposure was recognized early enough by the family to allow prophylaxis with albendazole. Because of the potential fatal or neurologically catastrophic effects of this disease immediate treatment is indicated. This is started in advance of environmental studies that are done to determine if the feces is indeed contaminated.

Glutathione Species And Metabolomic Prints In Subjects With Liver Disease As Biological Markers For The Detection Of Hepatocellular Carcinoma, Juan R. Sanabria, Rajan S. Kombu, Guo-Fang Zhang, Yana Sandlers, Jizhou Ai, Rafael A. Ibarra, Rime Abbas, Kush Goyal, Henri Brunengraber

Surgery

Background: The incidence of liver disease is increasing in USA. Animal models had shown glutathione species in plasma reflects liver glutathione state and it could be a surrogate for the detection of hepatocellular carcinoma (HCC).

Methods: The present study aimed to translate methods to the human and to explore the role of glutathione/metabolic prints in the progression of liver dysfunction and in the detection of HCC. Treated plasma from healthy subjects (n = 20), patients with liver disease (ESLD, n = 99) and patients after transplantation (LTx, n = 7) were analyzed by GC- or LC/MS. Glutathione labeling profile was …

A Novel Codon-Optimized Siv Gag-Pol Immunogen For Gene-Based Vaccination, Catherine M. Crosby, Eric A. Weaver, Reeti Khare, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Simian immunodeficiency virus (SIV) is a robust pathogen used in non-human primates to model HIV vaccines. SIV encodes a number of potential vaccine targets. By far the largest and most conserved protein target in SIV is its gag-pol protein that bears many epitopes to drive multivalent immune T cell responses. While gag-pol is an attractive antigen, it is only translated after a frame shift between gag and pol with the effect that gag and pol are expressed at an approximate 10/1 ratio. The codon bias of native lentiviral genes are also mismatched with the abundance of tRNAs in mammalian cells …

Genomics And Csf Analyses Implicate Thyroid Hormone In Hippocampal Sclerosis Of Aging, Peter T. Nelson, Yuriko Katsumata, Kwangsik Nho, Sergey C. Artiushin, Gregory A. Jicha, Wang-Xia Wang, Erin L. Abner, Andrew J. Saykin, Walter A. Kukull, Alzheimer’S Disease Neuroimaging Initiative (Adni), David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

We report evidence of a novel pathogenetic mechanism in which thyroid hormone dysregulation contributes to dementia in elderly persons. Two single nucleotide polymorphisms (SNPs) on chromosome 12p12 were the initial foci of our study: rs704180 and rs73069071. These SNPs were identified by separate research groups as risk alleles for non-Alzheimer’s neurodegeneration. We found that the rs73069071 risk genotype was associated with hippocampal sclerosis (HS) pathology among people with the rs704180 risk genotype (National Alzheimer’s Coordinating Center/Alzheimer’s Disease Genetic Consortium data; n = 2113, including 241 autopsy-confirmed HS cases). Furthermore, both rs704180 and rs73069071 risk genotypes were associated with widespread brain …

In The Postoperative Cardiothoracic Surgical Patient Being Mechanically Ventilated, Is There A Difference In Outcomes When Comparing Sedation With Dexmedetomidine Versus Propofol?, Benjamin Heinrich Riebesel

Doctoral Projects

Patients undergoing a cardiothoracic operation typically require mechanical ventilation in the postoperative phase. Each year approximately 395,000 of these operations are performed in the United States alone. As many as 10% of these patients require reoperation within the first few hours of recovery due to complications (Barash & Cullen, 2013). This comprehensive review of the literature was performed to determine whether postoperative sedation with dexmedetomidine leads to better patient outcomes than sedation with propofol. Inclusion criteria included publications written in the English language, articles available in full text, articles written within the last 10 years, and publications with a focus …

Adoption Of Perioperative Lidocaine Infusion For The Reduction Of Postoperative Pain, Brandon Scott Figueiredo

Doctoral Projects

Laparoscopic capability provides numerous benefits to patients requiring abdominal surgical procedures. However, the use of these techniques has presented the anesthesia provider with a unique set of challenges in terms of perioperative management and postoperative pain reduction. No standardized method has existed to reduce postoperative pain and improve recovery following these procedures. There were three primary goals of this project. The first goal was to conduct a meta-analysis of randomized controlled trials to determine the benefit of the use of intravenous lidocaine infusions to reduce postoperative pain in laparoscopic abdominal surgery. Twelve articles were included in the meta-analysis that pertained …

Oral Carbohydrate Administration Prior To Colorectal Surgery: Practice Change Outcomes And Economic Analysis, Joshua Kendrick Ezelle

Doctoral Projects

Difference in recovery times has been an interest of mine for many years. I observed that an open heart surgery routinely recovered and discharged on the third post-op day, while a colorectal patient often required a hospital stay of five to ten days. I began researching recovery methods of colorectal patients. I found enhanced recovery techniques like decreased narcotic, use of NSAID’s, early ambulation, and the use of medications that assist with bowel peristalsis are being employed nationally. Other techniques are now starting to be used with positive results. One of these is Carb-loading. Carb-loading is the oral intake of …

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

Evaluating Cardiovascular Dysfunction During Increased Activity And Exercise Rehabilitation Following Incomplete Thoracic Spinal Cord Injury In The Adult Rat., Kathryn A. Harman

Electronic Theses and Dissertations

Spinal cord injury (SCI) results in whole-body dysfunction. While the majority of SCI research is focused on improving locomotor function after injury, cardiovascular (CV) disease continues to be the leading cause of morbidity in the chronic SCI patient population. The combination of injury-induced destruction of autonomic pathways, maladaptive plasticity within lumbosacral circuits, and the progressive decline in physical fitness contribute to the poor CV status of SCI individuals. Currently, there is little emphasis on implementing appropriately-timed acute rehabilitation techniques aimed to curtail maladaptive remodeling and improve CV outcomes. Furthermore, no pre-clinical or clinical studies have investigated the most appropriate time-course …

Mir-155 Expression And Correlation With Clinical Outcome In Pediatric Aml: A Report From Children's Oncology Group., Ranjani Ramamurthy, Maya Hughes, Valerie Morris, Hamid Bolouri, Robert B. Gerbing, Yi-Cheng Wang, Michael R. Loken, Susana C. Raimondi, Betsy A. Hirsch, A S. Gamis, Vivian G. Oehler, Todd A. Alonzo, Soheil Meshinchi

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Aberrant expression of microRNA-155 (miR-155) has been implicated in acute myeloid leukemia (AML) and associated with clinical outcome.

PROCEDURE: We evaluated miR-155 expression in 198 children with normal karyotype AML (NK-AML) enrolled in Children's Oncology Group (COG) AML trial AAML0531 and correlated miR-155 expression levels with disease characteristics and clinical outcome. Patients were divided into quartiles (Q1-Q4) based on miR-155 expression level, and disease characteristics were then evaluated and correlated with miR-155 expression.

RESULTS: MiR-155 expression varied over 4-log10-fold range relative to its expression in normal marrow with a median expression level of 0.825 (range 0.043-25.630) for the entire …

Erratum To: High Expression Of Myocyte Enhancer Factor 2c (Mef2c) Is Associated With Adverse-Risk Features And Poor Outcome In Pediatric Acute Myeloid Leukemia: A Report From The Children's Oncology Group., George S. Laszlo, Todd A. Alonzo, Chelsea J. Gudgeon, Kimberly H. Harrington, Alex Kentsis, Robert B. Gerbing, Yi-Cheng Wang, Rhonda E. Ries, Susana C. Raimondi, Betsy A. Hirsch, A S. Gamis, Soheil Meshinchi, Roland B. Walter

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

A Generalized Framework For Computational Design And Mutational Scanning Of T-Cell Receptor Binding Interfaces, Timothy P. Riley, Cory M. Ayres, Lance M. Hellman, Nishant K. Singh, Michael Cosiano, Jennifer M. Cimons, Michael J. Anderson, Kurt H. Piepenbrink, Brian G. Pierce, Zhiping Weng, Brian M. Baker

Food for Health: Publications

T-cell receptors (TCRs) have emerged as a new class of therapeutics, most prominently for cancer where they are the key components of new cellular therapies as well as soluble biologics. Many studies have generated high affinity TCRs in order to enhance sensitivity. Recent outcomes, however, have suggested that fine manipulation of TCR binding, with an emphasis on specificity may be more valuable than large affinity increments. Structure-guided design is ideally suited for this role, and here we studied the generality of structure-guided design as applied to TCRs. We found that a previous approach, which successfully optimized the binding of a …

Development, Validation And Application Of A New Fornix Template For Studies Of Aging And Preclinical Alzheimer's Disease, Christopher A. Brown, Nathan F. Johnson, Amelia J. Anderson-Mooney, Gregory A. Jicha, Leslie M. Shaw, John Q. Trojanowski, Linda J. Van Eldik, Frederick A. Schmitt, Charles D. Smith, Brian T. Gold

Physical Therapy Faculty Publications

We developed a merged younger-older adult template of the fornix and demonstrated its utility for studies of aging and preclinical Alzheimer's disease (AD). In Experiment 1, probabilistic tractography was used to reconstruct the fornix in younger and older adults and successful streamlines were then averaged to create a merged template in standard space. The new template includes the majority of the fornix from the hippocampal formation to the subcallosal region and the thalamus/hypothalamus. In Experiment 2, the merged template was validated as an appropriate measure for studies of aging, with comparisons against manual tracing measures indicating identical spatial coverage in …

5-Hydroxymethylcytosine Localizes To Enhancer Elements And Is Associated With Survival In Glioblastoma Patients, Kevin C. Johnson, E. Andres Houseman, Jessica E. King, Katharine M. Von Herrmann, Camilo E. Fadu, Brock C. Christensen

Dartmouth Scholarship

Glioblastomas exhibit widespread molecular alterations including a highly distorted epigenome. Here, we resolve genome-wide 5-methylcytosine and 5-hydroxymethylcytosine in glioblastoma through parallel processing of DNA with bisulfite and oxidative bisulfite treatments. We apply a statistical algorithm to estimate 5-methylcytosine, 5-hydroxymethylcytosine and unmethylated proportions from methylation array data. We show that 5-hydroxymethylcytosine is depleted in glioblastoma compared with prefrontal cortex tissue. In addition, the genomic localization of 5-hydroxymethylcytosine in glioblastoma is associated with features of dynamic cell-identity regulation such as tissue-specific transcription and super-enhancers. Annotation of 5-hydroxymethylcytosine genomic distribution reveal significant associations with RNA regulatory processes, immune function, stem cell maintenance and …

Temporary Nerve Block At Selected Digits Revealed Hand Motor Deficits In Grasping Tasks, Aude Cateron, Kerry Mcpartlan, Christina Gioeli, Emily Reid, Matt Turturro, Barry Hahn, Cynthia Benson, Wei Zhang

Publications and Research

Peripheral sensory feedback plays a crucial role in ensuring correct motor execution throughout hand grasp control. Previous studies utilized local anesthesia to deprive somatosensory feedback in the digits or hand, observations included sensorimotor deficits at both corticospinal and peripheral levels. However, the questions of how the disturbed and intact sensory input integrate and interact with each other to assist the motor program execution, and whether the motor coordination based on motor output variability between affected and non-affected elements (e.g., digits) becomes interfered by the local sensory deficiency, have not been answered. The current study aims to investigate the effect of …

Translational Study Of Liver Cancer And Hypertrophy: Translich, Mauro Enrique Tun Abraham

Electronic Thesis and Dissertation Repository

Abstract

Background: Associating liver partition with portal vein ligation for staged-hepatectomy (ALPPS) is a technique for inducing accelerated hypertrophy in patients with insufficient future liver remnant (FLR). It remains unknown whether this hypertrophy may lead to rapid cancer cell dissemination and/or alteration of immune cell/function reconstitution in the FLR. We aimed to determine if the rapid hypertrophy during ALPPS procedure results in more circulating tumour cell (CTCs) dissemination and whether the FLR remains immunologically competent in patients with CRLM.

Methods: In our prospective, observational, 2-arm study, we assessed the utility of CTCs as an evaluation tool for disease dissemination. Moreover, …

Severe Mortality Impact Of The 1957 Influenza Pandemic In Chile., Gerardo Chowell, Lone Simonsen, Rodrigo Fuentes, Jose Flores, Mark A Miller, Cécile Viboud

Microbiology, Immunology, and Tropical Medicine Faculty Publications

INTRODUCTION: Epidemiological studies of the 1957 influenza pandemic are scarce, particularly from lower-income settings.

METHODS: We analyzed the spatial-temporal mortality patterns of the 1957 influenza pandemic in Chile, including detailed age-specific mortality data from a large city, and investigated risk factors for severe mortality impact across regions.

RESULTS: Chile exhibited two waves of excess mortality in winter 1957 and 1959 with a cumulative excess mortality rate of 12 per 10 000, and a ~10-fold mortality difference across provinces. High excess mortality rates were associated with high baseline mortality (R(2) =41.8%; P=.02), but not with latitude (P>.7). Excess mortality rates …

Functional Validation Of Novel Compound Heterozygous Variants In B3gat3 Resulting In Severe Osteopenia And Fractures: Expanding The Disease Phenotype., Florian Job, Shuji Mizumoto, Laurie Smith, Natario Couser, Ashley Brazil, Howard Saal, Melanie Patterson, Margaret Gibson, Sarah E. Soden, Neil A. Miller, Isabelle Thiffault, Carol J. Saunders, Shuhei Yamada, Katrin Hoffmann, Kazuyuki Sugahara, Emily G. Farrow

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: A new disease class of syndromes, described as linkeropathies, which are derived from defects in the glycosaminoglycan-linker region as well as glycosaminoglycan-side chains of proteoglycans is increasingly being recognized as a cause of human disease. Proteoglycans are an essential component of the extracellular matrix. Defects in the enzymatic process of proteoglycan synthesis broadly occur due to the incorrect addition of side chains. Previously, homozygous missense variants within the B3GAT3 gene encoding beta 1,3 glucuronyltransferase 3(GlcAT-I) responsible for the biosynthesis of glycosaminoglycans have been described in 7 individuals.

CASE PRESENTATION: In this study, a 4-year-old patient with a severe phenotype …

Accuracy Requirements And Uncertainties In Radiotherapy: A Report Of The International Atomic Energy Agency., Debbie Van Der Merwe, Jacob Van Dyk, Brendan Healy, Eduardo Zubizarreta, Joanna Izewska, Ben Mijnheer, Ahmed Meghzifene

Oncology Publications

BACKGROUND: Radiotherapy technology continues to advance and the expectation of improved outcomes requires greater accuracy in various radiotherapy steps. Different factors affect the overall accuracy of dose delivery. Institutional comprehensive quality assurance (QA) programs should ensure that uncertainties are maintained at acceptable levels. The International Atomic Energy Agency has recently developed a report summarizing the accuracy achievable and the suggested action levels, for each step in the radiotherapy process. Overview of the report: The report seeks to promote awareness and encourage quantification of uncertainties in order to promote safer and more effective patient treatments. The radiotherapy process and the radiobiological …

Administration Of Electroconvulsive Therapy For Depression Associated With Deep Brain Stimulation In A Patient With Post-Traumatic Parkinson's Disease: A Case Study, Miles G. Cunningham, Golnaz Yadollahikhales, Gordana Vitaliano, Craig Van Horne

Neurosurgery Faculty Publications

Background: Deep brain stimulation (DBS) has been shown to be effective for parkinsonian symptoms poorly responsive to medications. DBS is typically well-tolerated, as are the maintenance battery changes. Here we describe an adverse event during a battery replacement procedure that caused rapid onset of severe depression.

Case Presentation: The patient is a 58-year-old woman who was in a serious motor vehicle accident and sustained a concussion with loss of consciousness. Within weeks of the accident she began developing parkinsonian symptoms that progressively worsened over the subsequent 10 years. Responding poorly to medications, she received DBS, which controlled her movement symptoms. …

Radiation Oncology Quality And Safety Considerations In Low Resource Settings: A Medical Physics Perspective, Jacob Van Dyk, Ahmed Meghzifene

Oncology Publications

The last few years have seen a significant growth of interest in the global radiation therapy crisis. Various organizations have quantified the need and are providing aid in support of addressing the shortfalls existing in many low-to-middle income countries (LMICs). With the tremendous demand for new facilities, equipment and personnel, it is very important to recognize the quality and safety challenges and to address them directly. An examination of publications on quality and safety in radiation therapy indicates a consistency in a number of the recommendations; however, these authoritative reports were generally based on input from high-resourced contexts. Here we …