The initial value problem for a parabolic equation of arbitrary even order

Thesis (Ph.D.)--Boston Universit

Educational potential, underachievement, and cultural pluralism

Peer reviewedPublisher PD

The relationship between anaesthetic technique, clinicopathological characteristics and the magnitude of the postoperative systemic inflammatory response in patients undergoing elective surgery for colon cancer

Background/aim: The magnitude of the postoperative systemic inflammatory response (SIR) is now recognised to be associated with both short and long-term outcomes in patients undergoing surgery for colon cancer. During such surgery, it is unclear whether the anaesthetic regimens influence the magnitude of the postoperative SIR, independent of other factors. The aim of the present study was to examine the association between anaesthetic agents, clinicopathological characteristics and the magnitude of the postoperative SIR in patients undergoing elective surgery for colon cancer. Methods: Patients with colon cancer who underwent elective open or laparoscopic surgery between 2008 and 2016 (n = 409) were studied at a single center. The relationship between type of anaesthesia, surgical technique; open (n = 241) versus laparoscopic (n = 168) and clinicopathological characteristics was examined by using chi-square testing. The chi-square test was used to determine which anaesthetic group influences the POD 2 CRP for only patients undergoing elective open colon surgery. Results: The majority of patients were <75 years old, male, normal weight or obese, underwent open surgery and had regional anaesthesia, in particular an epidural approach. There was a significant association between type of anaesthesia and post-operative CRP on day 2 (p <0.001) in patients undergoing open surgery but not laparoscopic surgery. Other factors associated with type of anaesthesia included; year of operation (p <0.01), surgical technique (p <0.001), and preoperative dexamethasone (p <0.01). Conclusion: In patients undergoing surgery for elective colon cancer, the type of anaesthesia varied over time. The type of anaesthesia appears to influence the magnitude of the postoperative SIR on post-operative day 2 in open surgery but not laparoscopic surgery. Future work using prospective study design is required to better define this relationship

Use of molecular modeling and site-directed mutagenesis to define the structural basis for the immune response to carbohydrate xenoantigens

BACKGROUND: Natural antibodies directed at carbohydrates reject porcine xenografts. They are initially expressed in germline configuration and are encoded by a small number of structurally-related germline progenitors. The transplantation of genetically-modified pig organs prevents hyperacute rejection, but delayed graft rejection still occurs, partly due to humoral responses. IgV(H )genes encoding induced xenoantibodies are predominantly, not exclusively, derived from germline progenitors in the V(H)3 family. We have previously identified the immunoglobulin heavy chain genes encoding V(H)3 xenoantibodies in patients and primates. In this manuscript, we complete the structural analysis of induced xenoantibodies by identifying the IgV(H )genes encoding the small proportion of V(H)4 xenoantibodies and the germline progenitors encoding xenoantibody light chains. This information has been used to define the xenoantibody/carbohydrate binding site using computer-simulated modeling. RESULTS: The VH4-59 gene encodes antibodies in the V(H)4 family that are induced in human patients mounting active xenoantibody responses. The light chain of xenoantibodies is encoded by DPK5 and HSIGKV134. The structural information obtained by sequencing analysis was used to create computer-simulated models. Key contact sites for xenoantibody/carbohydrate interaction for V(H)3 family xenoantibodies include amino acids in sites 31, 33, 50, 57, 58 and the CDR3 region of the IgV(H )gene. Site-directed mutagenesis indicates that mutations in predicted contact sites alter binding to carbohydrate xenoantigens. Computer-simulated modeling suggests that the CDR3 region directly influences binding. CONCLUSION: Xenoantibodies induced during early and delayed xenograft responses are predominantly encoded by genes in the V(H)3 family, with a small proportion encoded by V(H)4 germline progenitors. This restricted group can be identified by the unique canonical structure of the light chain, heavy chain and CDR3. Computer-simulated models depict this structure with accuracy, as confirmed by site-directed mutagenesis. Computer-simulated drug design using computer-simulated models may now be applied to develop new drugs that may enhance the survival of xenografted organs

Attitudes towards the use of perioperative steroids in resectional colorectal cancer surgery in the UK: a qualitative study

Introduction: Resectional surgery remains the mainstay of treatment for colorectal cancer. A heightened postoperative systemic inflammatory response has been shown to correlate negatively with short/long-term outcomes. Perioperative steroid administration may help to alleviate this systemic inflammatory response. This survey has been carried out to assess current attitudes towards perioperative steroid use and to gauge interest in a randomised control trial in this area. Method: An internet-based survey consisting of 9 questions was circulated via email. Those responses from outside the United Kingdom were excluded. Result: 74 doctors from the United Kingdom, predominantly Consultant Anaesthetists (54%) responded to this survey. 77% gave some or all of their patients steroids, in 75% of cases at the discretion of the anaesthetist. The main perceived benefit was to reduce postoperative nausea and vomiting. Diabetics and those deemed at high risk of wound infection were the group in whom most respondents would be reluctant to give steroids. 32% of respondents had no concerns. 87% of respondents felt that that a randomised trial in this field would be of clinical interest with most respondents (58%) preferring a three-armed trial – no steroids vs low dose steroids vs high dose steroids. Conclusion: – This survey indicated that perioperative steroid use is currently widespread. Sufficient equipoise exists for a trial in this area with regard to examining the impact of dexamethasone on postoperative complications and the postoperative systemic inflammatory response. Respondents favoured a 3-armed trial – no steroids vs low-dose steroids vs high-dose steroids

Similarities in the immunoglobulin response and V(H )gene usage in rhesus monkeys and humans exposed to porcine hepatocytes

BACKGROUND: The use of porcine cells and organs as a source of xenografts for human patients would vastly increase the donor pool; however, both humans and Old World primates vigorously reject pig tissues due to xenoantibodies that react with the polysaccharide galactose α (1,3) galactose (αGal) present on the surface of many porcine cells. We previously examined the xenoantibody response in patients exposed to porcine hepatocytes via treatment(s) with bioartficial liver devices (BALs), composed of porcine cells in a support matrix. We determined that xenoantibodies in BAL-treated patients are predominantly directed at porcine αGal carbohydrate epitopes, and are encoded by a small number of germline heavy chain variable region (V(H)) immunoglobulin genes. The studies described in this manuscript were designed to identify whether the xenoantibody responses and the IgV(H )genes encoding antibodies to porcine hepatocytes in non-human primates used as preclinical models are similar to those in humans. Adult non-immunosuppressed rhesus monkeys (Macaca mulatta) were injected intra-portally with porcine hepatocytes or heterotopically transplanted with a porcine liver lobe. Peripheral blood leukocytes and serum were obtained prior to and at multiple time points after exposure, and the immune response was characterized, using ELISA to evaluate the levels and specificities of circulating xenoantibodies, and the production of cDNA libraries to determine the genes used by B cells to encode those antibodies. RESULTS: Xenoantibodies produced following exposure to isolated hepatocytes and solid organ liver grafts were predominantly encoded by genes in the V(H)3 family, with a minor contribution from the V(H)4 family. Immunoglobulin heavy-chain gene (V(H)) cDNA library screening and gene sequencing of IgM libraries identified the genes as most closely-related to the IGHV3-11 and IGHV4-59 germline progenitors. One of the genes most similar to IGHV3-11, V(H)3-11(cyno), has not been previously identified, and encodes xenoantibodies at later time points post-transplant. Sequencing of IgG clones revealed increased usage of the monkey germline progenitor most similar to human IGHV3-11 and the onset of mutations. CONCLUSION: The small number of IGV(H )genes encoding xenoantibodies to porcine hepatocytes in non-human primates and humans is highly conserved. Rhesus monkeys are an appropriate preclinical model for testing novel reagents such as those developed using structure-based drug design to target and deplete antibodies to porcine xenografts

Tracking Staphylococcus aureus in the intensive care unit using Whole-Genome Sequencing

Background: Staphylococcus aureus remains an important bacterial pathogen worldwide. This study utilized known staphylococcal epidemiology to track S. aureus between different ecological reservoirs in one ten-bed intensive care unit (ICU).Methods: Selected hand-touch surfaces, staff hands and air were systematically screened ten times during ten months, with patients screened throughout the study. S. aureus isolates were subjected to spa typing and epidemiological analyses, followed by wholegenome sequencing (WGS) to provide single nucleotide polymorphism (SNP) data.Results: Multiple transmission pathways between patients and reservoirs were investigated. There were 34 transmission events, of which 29 were highly related

Portfolio Vol. VI N 1

Wyman, John. Mrs. Brannon\u27s Bathtub . Prose. 1. Holbrook, Harold R. Sonnet . Poem. 7. Hayne, Barbara. Prayer of A Youth . Poem. 7. Egger, Ellen. An Evening . Poem. 7. Cuninggim, Merrimon. Lambda Pi Beta Mu . Prose. 9. Willett, Thelma. White Rosebuds . Poem. 11. Willett, Thelma. Span of A Life in Mine . Poem. 11. Willett, Thelma. Seventeen . Poem. 11. Willett, Thelma. Ave Atque Vale . Poem. 11. Willett, Thelma. The Ashes of Letters . Poem. 11. Miller, Albert. ...To One I Have Known and Loved . Prose. 12. Wyman, John. Browning the Artist . Prose. 14. Brannon, Pat. Revolution . Poem. 18. Forsberg, Nancy. Unnamed. Poem. 18. Kearns, Carolyn. A Co-Ed\u27s Wish . Poem. 18. Goetz, Marilyn. Fate\u27s Fury . Prose. 19. Harvey, Richard. Man Who Ate the Cheesecake . Prose. 21. Spike, Robert. Mechanikos . Poem. 22. Stodghill, Patricia. Anodyne . Poem. 23. Ladd, Donald. Torch-Light . Poem. 23

Portfolio Vol. VI N 2

Wyman, John. Mrs. Brannon\u27s Bathtub . Prose. 1. Holbrook, Harold R. Sonnet . Poem. 7. Hayne, Barbara. Prayer of A Youth . Poem. 7. Egger, Ellen. An Evening . Poem. 7. Cuninggim, Merrimon. Lambda Pi Beta Mu . Prose. 9. Willett, Thelma. White Rosebuds . Poem. 11. Willett, Thelma. Span of A Life in Mine . Poem. 11. Willett, Thelma. Seventeen . Poem. 11. Willett, Thelma. Ave Atque Vale . Poem. 11. Willett, Thelma. The Ashes of Letters . Poem. 11. Miller, Albert. ...To One I Have Known and Loved . Prose. 12. Wyman, John. Browning the Artist . Prose. 14. Brannon, Pat. Revolution . Poem. 18. Forsberg, Nancy. Unnamed. Poem. 18. Kearns, Carolyn. A Co-Ed\u27s Wish . Poem. 18. Goetz, Marilyn. Fate\u27s Fury . Prose. 19. Harvey, Richard. Man Who Ate the Cheesecake . Prose. 21. Spike, Robert. Mechanikos . Poem. 22. Stodghill, Patricia. Anodyne . Poem. 23. Ladd, Donald. Torch-Light . Poem. 23