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2016

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Cancer

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Comparative Evaluation Of Malnutrition Screening In Oncology Patients In An Acute Care Hospital: A Pilot Study, Chandni Sen Sinha Dec 2016

Comparative Evaluation Of Malnutrition Screening In Oncology Patients In An Acute Care Hospital: A Pilot Study, Chandni Sen Sinha

Master's Theses

Malnutrition is associated with negative health consequences in the vulnerable cancer population, making it imperative for an efficient interdisciplinary approach to conduct nutritional screening using an appropriate scale. For the present study, a comparison between an existing malnutrition risk-screening questionnaire (EMR-SQ) and a comprehensive screening questionnaire (CMR-SQ) was performed on 37 cancer patients. The first stage of data collection required the nurses to electronically complete the EMR-SQ. In the second stage, the same patients’ data were assessed using the CMR-SQ, developed by the authors based on the guidelines of the PG-SGA and A.S.P.E.N. The CMR-SQ identified 32.4% at low, 37.8% …


Preying On The Desperate, Karen M. Savage Dec 2016

Preying On The Desperate, Karen M. Savage

Capstones

In this story, I investigate the marketing and sale of concentrated hydrogen peroxide to individuals who are desperate to cure serious health maladies. The story follows an online marketer who was warned by the FDA more than ten years ago to stop claiming hydrogen peroxide ingestion could cure cancer and other ailments. But in spite of the warning and subsequent FDA investigation, the individual continues to claim high strength hydrogen peroxide helps with brain tumors and leukemia and he can now be tied to several different websites marketing various “brands” of high strength hydrogen peroxide. Another marketer distributes hydrogen peroxide …


Development Of Cxcr4-Inhibiting Nanoparticles For The Treatment Of Metastatic Cancer, Yan Wang Dec 2016

Development Of Cxcr4-Inhibiting Nanoparticles For The Treatment Of Metastatic Cancer, Yan Wang

Theses & Dissertations

Metastasis is the main cause of cancer mortality and morbidity, leading to several million deaths every year. Less than 20% of pancreatic cancer (PC) patients are candidates for surgery due to spread beyond the pancreas. Desmoplasia presents substantial barriers to perfusion, diffusion, and convection of antitumor therapeutics into the PC tissues. We focus on developing novel therapies that regulates tumor microenvironment, chemosensitizing tumor to therapeutics and preventing metastasis.

Gene therapy is emerging as a promising new therapeutic agents for cancer treatment. A targeted, systemic, effective and safe gene delivery system should be developed. CXCR4/SDF-1 axis plays a crucial role in …


The Human Arf Tumor Suppressor Regulates Drosha Nucleolar Localization And Rrna Processing Activity, Sree Chandana Sridhar Yaddanapudi Dec 2016

The Human Arf Tumor Suppressor Regulates Drosha Nucleolar Localization And Rrna Processing Activity, Sree Chandana Sridhar Yaddanapudi

Arts & Sciences Electronic Theses and Dissertations

Ribosomes are vital to the survival of a cell, as they are directly responsible for the synthesis of proteins, which perform critical cellular functions. As such, majority of the energy reserves in a proliferating cell are expended towards synthesis of ribosomes. Cancer cells, with their enhanced proliferation rates, tend to upregulate ribosome biogenesis in order to meet the demand for increased protein synthesis necessary to sustain rapid proliferation. Many of the oncogenes and tumor suppressors known to be deregulated in cancers are capable of positively and negatively regulating ribosome biogenesis, respectively. The ARF tumor suppressor strongly suppresses ribosome biogenesis, particularly …


Comprehensive Molecular Characterization Of Human Nodal, Scott D. Findlay Dec 2016

Comprehensive Molecular Characterization Of Human Nodal, Scott D. Findlay

Electronic Thesis and Dissertation Repository

Nodal and related ligands are highly conserved members of the TGF-beta superfamily with well-established and essential roles in the early embryonic development of vertebrates, and in cell fate decisions in human embryonic stem (hES) cells. Aberrant NODAL signaling also generally promotes pro-tumourigenic phenotypes and the progression of a wide array of human cancers. Despite being pursued as a potential therapeutic target, many aspects of NODAL’s molecular biology remain poorly understood. This thesis provides a comprehensive characterization of gene expression from the human NODAL locus at multiple levels. First, an intronic NODAL SNP known as rs2231947 was found to be functional …


Dose-Related Sex Differences In The Establishment Of Conditioned Disgust (Anticipatory Nausea), And The Effect Of Peripubertal And Adult Immune System Stimulation With The Endotoxin Lipopolysaccharide (Lps) On Learning And Memory In The Rat, Caylen J. Cloutier Dec 2016

Dose-Related Sex Differences In The Establishment Of Conditioned Disgust (Anticipatory Nausea), And The Effect Of Peripubertal And Adult Immune System Stimulation With The Endotoxin Lipopolysaccharide (Lps) On Learning And Memory In The Rat, Caylen J. Cloutier

Electronic Thesis and Dissertation Repository

This thesis examined sex differences in the establishment of lithium chloride (LiCl) – induced conditioned disgust behavior (anticipatory nausea) to a distinct context, as well as, the establishment of conditioned place avoidance (CPA) using rodent models. Also examined were potential sex differences in response to treatment with the bacterial endotoxin, lipopolysaccharide (LPS), and its effect on learning and memory. In Chapter 2, male and female naïve Long-Evans rats were injected (intraperitoneally; i.p.) with either 200 µg/kg LPS or 0.9% (NaCl), 90 minutes prior to i.p. injections of either 128 mg/kg LiCl or 0.9% NaCl, and immediately placed into a distinctive …


Synthesis And Biological Evaluation Of Fluorescein-Tagged Carborane For Boron Neutron Capture Therapy (Bnct), Lucas A. Kuzmanic Dec 2016

Synthesis And Biological Evaluation Of Fluorescein-Tagged Carborane For Boron Neutron Capture Therapy (Bnct), Lucas A. Kuzmanic

Honors Capstones

Boron Neutron Capture Therapy (BNCT) is a bimodal cancer treatment that involves killing cancer cells through a nuclear reaction of two nontoxic species, boron-10 (10B) and thermal neutrons. There are currently only two FDA-approved drugs for this promising area of cancer therapy, so present research focuses on the synthesis of novel compounds with high boron content as well as methods for their delivery into the tumor cell. A fluorescent tag can allow the observation of the delivery vehicle’s uptake during biodistribution studies. Accordingly, fluorescein was conjugated with iodinated 1-methyl-o-carborane and characterized using Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy …


Til Death Did Us Part, The Story Of The Health And Death Of Franklin Delano Roosevelt, Mary E. Edgecomb Dec 2016

Til Death Did Us Part, The Story Of The Health And Death Of Franklin Delano Roosevelt, Mary E. Edgecomb

Graduate Theses

The awe of celebrity, including presidents, creates the impression of beings who are larger than life, without the problems of the common man. Franklin D. Roosevelt, unbeknownst to many Americans, had significant health issues. These health issues predate his paralytic illness and worsened during his presidency. Efforts to maintain his image as the unconquerable president of the United Sates led to concealment of these problems and, in turn, negatively impacted his medical care. While most previous studies focused on individual health issues, this research will show a continuum of medical problems that not only impacted his presidency but also were …


The Waiting House, Erika Marie Mueller Dec 2016

The Waiting House, Erika Marie Mueller

Theses and Dissertations

The poems in this collection, The Waiting House, use techniques associated with an evolving elegiac tradition in their portrayal of anticipatory grief born of terminal illness and impending loss. Like the melancholic mourning of modern elegies described by Jahan Ramazani, my poems often resist consolation even as they borrow from elegiac conventions like poetic substitution and repetition. Additionally, they utilize strategies and patterns of literary anger outlined by Alicia Suskin Ostriker as common in postwar American women’s poetry, to express anger that is also anticipatory grief. Finally, this collection uses illness metaphors to question the well being of a larger …


Elucidating The Effects Of Metabolic State On Nanoparticle Distribution In Mice And In Vitro Uptake, Kevin James Quigley Dec 2016

Elucidating The Effects Of Metabolic State On Nanoparticle Distribution In Mice And In Vitro Uptake, Kevin James Quigley

Doctoral Dissertations

Since almost 70% of the U.S. population over 20 years old is overweight and 30% is obese, with much of the western world following suit, many patients that will potentially be administered circulating nanoparticles designed to localize to tumors and avoid non-target areas will have significant amounts of white adipose tissue (WAT), enlarged livers, and additional metabolic complications such as type 2 diabetes. However, studies on nanoparticle biodistribution and efficacy take place almost without exception in lean rodents with healthy metabolic states. In this work, I determined the biodistribution of model nanoparticles – neutral filomicelles and polystyrene spheres both carrying …


The Oncolytic Potential Of Tanapoxvirus To Treat Retinoblastoma, John D. Christie Dec 2016

The Oncolytic Potential Of Tanapoxvirus To Treat Retinoblastoma, John D. Christie

Masters Theses

Retinoblastoma is the leading cause of intraocular malignancy in children under 2 years of age. Current treatments, while generally effective in eliminating the tumor, have many negative side effects. Oncolytic virotherapy is the use of either wild type or recombinant viruses, to destroy tumor cells. There are currently several viruses being engineered as potential therapeutics for a wide range of cancers. They offer tumor specific alternative to current therapies with lesser toxicity. This study looked at the oncolytic efficacy of multiple tanapoxviruses (TPV) recombinants in an in vitro retinoblastoma. Here we have tested recombinants of TPV for their ability to …


Establishing A Clinically Relevant Mouse Model Of Human Aml To Test Novel Transmethylation Inhibitors., Aditya Barve Dec 2016

Establishing A Clinically Relevant Mouse Model Of Human Aml To Test Novel Transmethylation Inhibitors., Aditya Barve

Electronic Theses and Dissertations

Acute myeloid leukemia (AML) is a highly heterogeneous clonal disorder characterized by an accumulation of malignant immature myeloid progenitors in the bone marrow (BM) that hinder normal hematopoiesis. Patient AML exhibits a dramatic heterogeneity in terms of cytogenetics, disease morphology, and associated prognoses and/or chemotherapeutic sensitivity. Thus it becomes clearly evident that the investigation of novel therapeutics for AML will require model systems that are capable of recapitulating this stark heterogeneity in a patient specific manner. Furthermore, it is now understood that the surrounding bone marrow (BM) microenvironment and supporting cells play a critical role in leukemic progression as well …


The Role Of Viral Interleukin-6 In Tumor Development Of Kaposi's Sarcoma-Associated Herpesvirus Lymphomas, Rebecca A. Fullwood Dec 2016

The Role Of Viral Interleukin-6 In Tumor Development Of Kaposi's Sarcoma-Associated Herpesvirus Lymphomas, Rebecca A. Fullwood

Theses and Dissertations

Kaposi's sarcoma herpesvirus (KSHV) is a cancer-causing virus, primarily affecting AIDS patients. KSHV is found in 3-10% of the U.S. population and can cause a range of cancers in the highly immunosuppressed; these cancers include Kaposi's sarcoma, pleural effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). The current techniques for treating these cancers are relatively ineffective, largely due to their inefficiency at targeting tumors formed by the infection. One protein produced by KSHV, the viral homolog of interleukin-6 (vIL-6), is thought to play a major role in tumor development post-infection. Here a novel animal model is implemented to study the …


Characterizing Colorectal Cancer Cells And Their Interactions With Polymethoxyflavones By Raman Microscopy, Hua Zhang Nov 2016

Characterizing Colorectal Cancer Cells And Their Interactions With Polymethoxyflavones By Raman Microscopy, Hua Zhang

Doctoral Dissertations

Polymethoxyflavones (PMFs), especially Nobiletin (NBT) and 5-demethylnobiletin (5DN), have been widely studied and proved to have anti-cancer effects. However, their exact modes of action against cancer cells are not fully understood. Raman spectroscopy is a molecular vibrational spectroscopy can be used to measure overall biochemical function of single cells noninvasively and without adding any chemical labels. Herein, we characterized the cellular responses of human colorectal cancer HT29 and HCT116 cells, that grow on the gold coated slides, to the treatments of NBT and 5DN using Raman microscopy. Raman microscopic images obtained indicated the different modes of action of these two …


The Lived Experience Of Fathers With Advanced Cancer, Maria Mowassee Sep 2016

The Lived Experience Of Fathers With Advanced Cancer, Maria Mowassee

Dissertations, Theses, and Capstone Projects

Historically, fathers have been neglected as a research population in the nursing and oncology literature. This was in relation to their role being viewed as a disciplinarian and breadwinner instead of a nurturer. Fast-forward to modern day society, their role has evolved into a more involved parent that is necessary for their child’s development and well-being. The literature has also evolved and in recent years, this population has been gaining recognition and it is of great importance to understand their role, perception, and concerns as it pertains to being involved fathers. Therefore, when considering fathers with advanced cancer when death …


Characterization Of The Catalytic Ck2 Subunits With Substitutions At Residues Involved In Inhibitor Binding, Paul Desormeaux Sep 2016

Characterization Of The Catalytic Ck2 Subunits With Substitutions At Residues Involved In Inhibitor Binding, Paul Desormeaux

Electronic Thesis and Dissertation Repository

CK2 is a constitutively active, ubiquitously expressed and pleiotropic serine/threonine protein kinase that is implicated in many cellular functions including tumorigenesis. CK2 has two catalytic subunits, CK2a and CK2a’, that carry out its function in the cell. Previous studies have indicated that inhibitor-refractory mutants have been effective in recovering residual CK2 activity, in the presence of inhibitors, when compared to wild type CK2. Based on these observations, inhibitor-refractory mutants were created for both CK2a and CK2a’ and tested with various concentrations with two CK2-specific inhibitors, CX-4945 and inhibitor VIII. The CK2a triple mutant (V66A/I174A/H160D) was tested in inducible U2OS Flp-In …


Longitudinal Evaluation Of Patient Concerns After Surgery For Head And Neck Cancer, Isabel Wozniczka Sep 2016

Longitudinal Evaluation Of Patient Concerns After Surgery For Head And Neck Cancer, Isabel Wozniczka

Electronic Thesis and Dissertation Repository

The primary purpose of this study was to investigate and describe the longitudinal effects of shoulder and neck mobility, strength, and quality of life (QOL) following neck dissection (ND) surgery and identify the concerns of head and neck cancer (HNC) patients. ND is one of the standard procedures for treating HNC, which results in many complications and dysfunctions that can have an effect on a patient’s QOL.

The study had 27 eligible HNC participants who underwent ND, of which eight participated in the shoulder range of motion (ROM) and strength and 12 participated in the QOL patient-reported outcomes analysis. The …


Sleep Disruption Among Cancer Patients Following Autologous Hematopoietic Stem Cell Transplantation, Ashley M. Nelson Sep 2016

Sleep Disruption Among Cancer Patients Following Autologous Hematopoietic Stem Cell Transplantation, Ashley M. Nelson

USF Tampa Graduate Theses and Dissertations

Background: Sleep disruption is one of the most commonly reported quality of life concerns among cancer patients who have undergone hematopoietic stem cell transplantation (HSCT). Despite the high percentage of patients reporting sleep concerns, relatively little research has characterized sleep problems or explored relationships with psychological factors. In addition, no studies have used actigraph technology to characterize sleep issues among transplant recipients.

Method: Autologous HSCT recipients who were 6 to 18 months post-transplant were invited to participate. Patients completed self-report measures of cancer-related distress, fear of cancer recurrence, dysfunctional cognitions about sleep, and maladaptive sleep behaviors upon enrollment, wore an …


Beliefs About Animal Assisted Interventions Among Medical Social Workers, Gyda D. Boyd Sep 2016

Beliefs About Animal Assisted Interventions Among Medical Social Workers, Gyda D. Boyd

Electronic Theses, Projects, and Dissertations

Animal‑Assisted Intervention (AAI) is used to significantly reduce pain, lower blood pressure, decrease anxiety, and help ease depression in people with a range of health problems; however, it is not readily used in the hospital setting. Research involving the Human‑Animal Bond (HAB) is well established, yet most social workers receive no special training or coursework about this topic as it applies to working with patients or consumers. This study sought to understand the beliefs about AAI among medical social workers in healthcare settings in order to gauge what knowledge and degree of exposure they may have had to AAI. Eighteen …


Psychological Aspects Of Head And Neck Cancer, Katherine Rieke Aug 2016

Psychological Aspects Of Head And Neck Cancer, Katherine Rieke

Theses & Dissertations

Patients with head and neck cancer may be at increased risk for depression diagnosis when compared to other cancer sites, both before and after their cancer diagnosis. Behavioral risk factors for head and neck cancers, including tobacco and alcohol use, may be indicative of depression before cancer diagnosis. Further, head and neck cancers and their treatments can cause serious morbidity among patients, including physical disfigurement and loss of function. Additionally, these cancers are often accompanied by social stigma, personal shame, and guilt. While there is a significant body of research examining depression in this cancer population, there are still several …


Survival Analysis In A Clinical Setting, Yunzhao Liu Aug 2016

Survival Analysis In A Clinical Setting, Yunzhao Liu

Arts & Sciences Electronic Theses and Dissertations

With the fast paced advancement of modern medicine, cancer treatments have improved greatly over the past few decades; however, the overall survival rate has not improved for head neck squamous cell carcinoma (HNSCC). Traditionally, the general affected population of HNSCC was male over 50-60 years of age, whom have had history of alcohol and tobacco use. Conversely, in the recent decades, HNSCC has exhibited significant rise in younger patients, largely due to the increase in human papillomavirus (HPV) infection among young adults.

Generally, HPV as the most prevalent sexually transmitted disease, consisted of strains that do not cause harm to …


The P38mapk-Mk2-Hsp27 Axis Regulates The Mrna Stability Of The Pro-Tumorigenic Senescence-Associated Secretory Phenotype, Hayley Reynolds Moore Aug 2016

The P38mapk-Mk2-Hsp27 Axis Regulates The Mrna Stability Of The Pro-Tumorigenic Senescence-Associated Secretory Phenotype, Hayley Reynolds Moore

Arts & Sciences Electronic Theses and Dissertations

Protecting the genome is a vital aspect of safeguarding organismal health. Inability to efficiently and effectively replicate the genome or repair damage the genome may encounter can lead to mutational accumulation or senescence, both of which are drivers of multiple diseases including cancer. Understanding the mechanisms by which the genome is maintained, as well as the consequences of repeated rounds of replication or exposure to DNA damaging agents, will allow for greater understanding of the diseases they promote as well as development of targeted therapies aimed at mitigating the detrimental effects of genomic insult. The first section of my work …


State Space Analysis Of Dominant Structures In Dynamic Social Systems, Jeremy B. Sato Aug 2016

State Space Analysis Of Dominant Structures In Dynamic Social Systems, Jeremy B. Sato

McKelvey School of Engineering Theses & Dissertations

Many systems involving human relationships are modeled as dynamic systems, as diverse as urban population growth, diffusion of innovations, spread of viruses, and supply chain management. A fundamental assumption is that these systems contain variables which accumulate and deplete over time (people, innovation adoptions, infections, and orders), and whose dynamics are determined by societal rules and human decision making processes. These assumptions allow the system to be formally expressed by ordinary differential equations which are often nonlinear and contain multiple state variables and feedback loops. Analytical methods have been developed to identify the dominant feedback loops which primarily influence the …


Identifying Inflammatory Bowel Disease Patients In Tcga Database, Regina Chang Aug 2016

Identifying Inflammatory Bowel Disease Patients In Tcga Database, Regina Chang

Mathematics Theses

Chronic inflammation increases the risk of developing cancer. We aim to investigate the molecular pathway of inflammation induced cancer by comparing gene expression in colorectal (CRC) tumors of patients with inflammatory bowel disease (IBD) to sporatic colorectal tumors. Since mRNA microarray data of IBD induced CRC is not readily available, we attempt to isolate IBD patients in a public database based on their gene expression signatures.


Psychometric Properties Of Three Common Depression Measures In Breast Cancer Patients With Major Depressive Disorder, Audrey Ashton File Aug 2016

Psychometric Properties Of Three Common Depression Measures In Breast Cancer Patients With Major Depressive Disorder, Audrey Ashton File

Doctoral Dissertations

Breast cancer is the most frequently diagnosed cancer among women in the United States and MDD is the most common mental health problem in women with breast cancer. There is lack of research on measures of depression in this population. This study examined the psychometric properties of three commonly used depression measures, the BDI-II, CES-D, and HRSD, with clinically depressed breast cancer patients (n = 127). Findings revealed the measures displayed good distributional characteristics, internal consistency, and convergent validity. Discriminative validity with the BAI was not demonstrated, however, and confirmatory factor analyses indicated that the existing models of these …


The Roles Of Nuclear Receptor Nr4a1 In Cancer Cell Proliferation And Skeletal Muscle Differentiation, Alexa Farmer Aug 2016

The Roles Of Nuclear Receptor Nr4a1 In Cancer Cell Proliferation And Skeletal Muscle Differentiation, Alexa Farmer

Theses and Dissertations (ETD)

Nuclear receptors (NRs) constitute a major class of drug targets in the treatment of various cancer types. NRs respond to cellular signals and become activated upon ligand binding to transcriptionally modulate expression of target genes. NR4A1 (Nur77) is a member of the NR4A family of nuclear receptors and displays an oncogenic profile in many cancer models. It is often upregulated in adult solid malignancies and is known to promote cell proliferation and survival. Knockdown studies of NR4A1 in cancer cell lines results in decreased cell growth and angiogenesis and increased apoptosis, suggesting NR4A1 is an oncogenic protein. Due to the …


Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez Aug 2016

Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez

Dissertations & Theses (Open Access)

Cancer is one of the leading causes of death and disease in the world. Considerable resources are spent to study and understand cancer, with the hope of developing new treatments and eventually cures that will help millions of people. Efforts to understand cancer are hindered by its inherent complexity and instability. Nonetheless, understanding the basics of tumor development and progression are the key to focused on studying the role of ΔNp63 in cancer, a p53 family member known to be involved in epithelial development, microRNA biogenesis, and stem cell maintenance. Using the strength of in vivo mouse models, we found …


Life Balance In Adult Healthy Siblings Of Individuals With Childhood Cancer., Yolanda Williams Aug 2016

Life Balance In Adult Healthy Siblings Of Individuals With Childhood Cancer., Yolanda Williams

Electronic Theses and Dissertations

Siblings of children who were diagnosed with cancer in childhood experience significant stress and psychological difficulties as a result of the cancer. Furthermore, the needs of siblings have often been overlooked in the cancer literature, prompting the need for more studies. The purpose of this dissertation is to examine the life balance and social support outcomes of adults who grew up in the household with a sibling that was diagnosed with cancer. The study sample consisted of 120 adult healthy siblings who grew up in a household with a sibling that was diagnosed with cancer prior to age 19. Participants …


The Discovery Of A Novel, Ras-Mediated Nore1a/Pmliv Tumor Suppressor Complex., Jessica Mezzanotte Sharpe Aug 2016

The Discovery Of A Novel, Ras-Mediated Nore1a/Pmliv Tumor Suppressor Complex., Jessica Mezzanotte Sharpe

Electronic Theses and Dissertations

Ras is the most commonly activated oncogene in human cancer. Activated Ras drives cell growth and proliferation by activating multiple mitogenic signaling pathways. However, Ras also has the paradoxical ability to promote anti-growth, pro-apoptotic, and pro-senescent signaling. The signaling pathways of many of these biological effectors remain poorly defined. One group of proteins capable of promoting Ras-induced apoptosis and cell cycle arrest is the RASSF family of tumor suppressors. Novel Ras Effector 1A, or NORE1A, was the first member of this family discovered and is a bona fide tumor suppressor that is lost or inactivated in a number of different …


Chemotherapy Induced Neutropenia And Increased Risk For Sepsis, Megan E. Moore-Weber Jul 2016

Chemotherapy Induced Neutropenia And Increased Risk For Sepsis, Megan E. Moore-Weber

Nursing Student Class Projects (Formerly MSN)

Available treatment options for patients diagnosed with cancer include surgery, the administration of chemotherapeutic agents, radiation therapy, or a combination of these modalities. Chemotherapeutic agents utilized to treat cancer have a variety of potential side effects. One of the most common and well known side effects associated with the administration of chemotherapeutic agents is neutropenia. Neutropenia places oncology patients at an increased risk of contracting infections which may lead to a life threatening complication known as sepsis. Sepsis is an extremely dangerous oncologic emergency requiring prompt medical treatment. Failure to recognize symptoms associated with sepsis in the neutropenic patient and …