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Peter Skelsey, Sonia N Humphris, Emma J Campbell, Ian K Toth
Potato blackleg and soft rot caused by Pectobacterium and Dickeya species are among the most significant bacterial diseases affecting potato production globally. In this study we estimate the impact of future temperatures on establishment of non-indigenous but confirmed Pectobacterium and Dickeya species in Great Britain (GB). The calculations are based on probabilistic climate change data and a model fitted to disease severity data from a controlled environment tuber assay with the dominant potato blackleg and soft rot-causing species in GB (P...
2018: PloS One
Michael A Iacocca, Joana R Chora, Alain Carrié, Tomáš Freiberger, Sarah E Leigh, Joep C Defesche, C Lisa Kurtz, Marina T DiStefano, Raul D Santos, Steve E Humphries, Pedro Mata, Cinthia E Jannes, Amanda J Hooper, Katherine A Wilemon, Pascale Benlian, Robert O'Connor, John Garcia, Hannah Wand, Lukáš Tichy, Eric J Sijbrands, Robert A Hegele, Mafalda Bourbon, Joshua W Knowles
Accurate and consistent variant classification is imperative for incorporation of rapidly developing sequencing technologies into genomic medicine for improved patient care. An essential requirement for achieving standardized and reliable variant interpretation is data sharing, facilitated by a centralized open-source database. Familial hypercholesterolemia (FH) is an exemplar of the utility of such a resource: it has a high incidence, a favorable prognosis with early intervention and treatment, and cascade screening can be offered to families if a causative variant is identified...
November 2018: Human Mutation
Matthew P Humphries, Stephen McQuaid, Stephanie Craig, Victoria Bingham, Perry Maxwell, Manisha Maurya, Fiona McLean, James Sampson, Patricia Higgins, Christine Greene, Jacqueline James, Manuel Salto-Tellez
INTRODUCTION: Patient suitability to anti-PD-L1 immune checkpoint inhibition is key to the treatment of non-small cell lung cancer (NSCLC). We present, applied to PD-L1 testing: a comprehensive cross-validation of two immunohistochemistry (IHC) clones; our descriptive experience in diagnostic reflex testing; the concordance of IHC to in-situ RNA (RNA-ISH); and application of digital pathology. METHODS: 813 NSCLC tumour samples collected from 564 diagnostic samples were analysed prospectively and 249 diagnostic samples analysed retrospectively in TMA format...
October 5, 2018: Journal of Thoracic Oncology
Andrew G Rudikoff, T Kent Ganocy, Kartik Kansagra, Fernando A Torres, Bridgette D Humphries, Antonio Hernandez Conte
No abstract text is available yet for this article.
September 11, 2018: Journal of Cardiothoracic and Vascular Anesthesia
Darcey Black, Sarah Brockbank, Simon Cruwys, Kim Goldenstein, Peter Hein, Bob Humphries
Nonalcoholic steatohepatitis (NASH) is emerging as a major public health issue for the 21st century and is associated with significant liver-related morbidity and mortality. At present, there are no approved drug therapies for NASH. Consequently, NASH has become the focus of significant public and private research and development. In this review, we highlight the research and development (R&D) challenges and opportunities in this emerging therapeutic area. In particular, we consider the impact of the development of new biomarker strategies on clinical trial execution and design, and the positioning of single and combination therapies in future approaches to the treatment of NASH...
October 3, 2018: Drug Discovery Today
Patricia J Simner, Yehudit Bergman, Marisol Trejo, Ava A Roberts, Remy Marayan, Tsigereda Tekle, Shelley Campeau, Abida Kazmi, Drew Bell, Shawna Lewis, Pranita D Tamma, Romney Humphries, Janet A Hindler
Background: Limited methods for colistin minimum inhibitory concentration (MIC) determination are available to clinical microbiology laboratories. The purpose of this study was to evaluate the accuracy of the colistin broth disk elution (CBDE) test as compared to broth microdilution (BMD) for identifying colistin MICs. Methods: CBDE was compared to colistin BMD using a collection of Gram-negative bacilli tested at two U.S. microbiology laboratories. Isolates tested included 121 retrospective clinical isolates, 45 prospective clinical isolates, and 6 mcr-1 positive E...
October 3, 2018: Journal of Clinical Microbiology
Junxin Wang, Ananthakrishnan Soundaram Jeevarathinam, Kathryn Humphries, Anamik Jhunjhunwala, Fang Chen, Ali Hariri, Bill Miller, Jesse V Jokerst
We recently reported a real-time method to measure heparin in human whole blood based on the photoacoustic change of methylene blue (MB). Intriguingly, the MB behaved unlike other "turn on" photoacoustic probes-the absorbance decreased as the photoacoustic signal increased. The underlying mechanism was not clear and motivated this study. We studied the binding mechanism of MB and heparin in water and phosphate buffer saline (PBS) with both experimental and computational methods. We found that the photoacoustic enhancement of the MB-heparin mixture was a result of MB-heparin aggregation due to charge neutralization and resulting sequestration of MB in these aggregates...
October 3, 2018: Bioconjugate Chemistry
Mira K Marchioretto, Jacqueline T Horton, Calvin A Berstler, Joseph B Humphries, Isaac J Koloditch, Samuel D Voss, Kimberly de La Harpe, Barry W Hicks, Latisha R Jefferies
Förster resonance energy transfer (FRET) is the basis for many techniques used in biomedical research. Due to its wide use in molecular sensing, FRET is commonly introduced in many biology, chemistry, and physics courses. While FRET is of great importance in the biophysical sciences, the complexity and difficulty of constructing FRET experiments has resulted in limited usage in undergraduate laboratory settings. Here, we present a practical undergraduate laboratory experiment for teaching FRET using a diverse set of green-emitting fluorescent proteins (FPs) as donors for a cross-linked Yukon orange FP...
October 3, 2018: Biochemistry and Molecular Biology Education
G Humphris, Y Yang, L Barracliffe, J Cameron, C Bedi
Fears of cancer recurrence (FCR) in patients with breast cancer may develop during radiotherapy. Radiographer communication with their patients may influence early survivorship FCR level. AIM: To investigate the management of emotional talk in patients with breast cancer attending their initial review appointments during radiotherapy and predict FCR at 6-8 weeks follow-up. METHODS: A mixed-methods observational study was conducted. Patients (consecutive sample, n = 60) with breast cancer, attending a major Scottish cancer centre, had their first two review appointments with their therapeutic radiographer (TR) audio-recorded...
October 1, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Marta Futema, Mafalda Bourbon, Maggie Williams, Steve E Humphries
Mutations in any of three genes (LDLR, APOB and PCSK9) are known to cause autosomal dominant FH, but a mutation can be found in only ∼40% of patients with a clinical diagnosis of FH. In the remainder, a polygenic aetiology may be the cause of the phenotype, due to the co-inheritance of common LDL-C raising variants. In 2013, we reported the development of a 12-SNP LDL-C "SNP-Score" based on common variants identified as LDL-C raising from genome wide association consortium studies, and have confirmed the validity of this score in samples of no-mutation FH adults and children from more than six countries with European-Caucasian populations...
October 2018: Atherosclerosis
Morgan Hakki, Romney M Humphries, Peera Hemarajata, Gregory B Tallman, Ryan K Shields, Roberta T Mettus, Yohei Doi, James S Lewis
Background: In Pseudomonas aeruginosa, fluoroquinolone exposure promotes resistance to carbapenems through up-regulation of efflux pumps and transcriptional down-regulation of the porin OprD. Evidence of this effect among hematologic malignancy (HM) patients or hematopoietic-cell transplant (HCT) recipients receiving fluoroquinolone prophylaxis for neutropenia is lacking. Methods: We retrospectively evaluated episodes of P. aeruginosa bloodstream infections in HM patients or HCT recipients over a 7-year period at our institution...
September 26, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Mara van Beusekom, Josie Cameron, Carolyn Bedi, Elspeth Banks, Tom Kelsey, Gerry Humphris
Background: Many patients who have been treated for breast cancer experience high levels of fear that the cancer will return. The FORECAST pilot study showed that for a third of the patients, fears of cancer recurrence (FCR) increase during radiotherapy treatment and that conversations with their therapeutic radiographer at the weekly review meetings might help patients manage these concerns. This study aims to develop a communication skills training package (KEW, for 'Know', 'Encourage' and 'Warm-up') for therapeutic radiographers based on the findings of the FORECAST pilot study and on active input from patients and radiographers...
2018: Pilot and Feasibility Studies
Martha H Mackay, Pamela A Ratner, Gerry Veenstra, Frank X Scheuermeyer, Maja Grubisic, Krishnan Ramanathan, Craig Murray, Karin H Humphries
BACKGROUND: Investigators have identified important racial-identity/ethnicity-based differences in some aspects of acute coronary syndrome (ACS) care and outcomes (time to presentation, symptoms, receipt of coronary angiography/revascularization, repeat revascularization, mortality). Patient-based differences such as pathophysiology and treatment-seeking behaviour account only partly for these outcome differences. We sought to investigate whether there are racial-identity/ethnicity-based variations in the initial emergency department (ED) triage and care of patients with suspected ACS in Canadian hospitals...
September 17, 2018: Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine
Lao-Tzu Allan-Blitz, Olivia L Ellis, Robert Bolan, Peera Hemarajata, Romney M Humphries, Akbar Shahkolahi, Mark McGrath, Jeffrey D Klausner
No abstract text is available yet for this article.
September 13, 2018: Sexually Transmitted Diseases
Jonathan D Humphries, Megan R Chastney, Janet A Askari, Martin J Humphries
Integrin adhesion complexes (IACs) have evolved over millions of years to integrate metazoan cells physically with their microenvironment. It is presumed that the simultaneous interaction of thousands of integrin receptors to binding sites in anisotropic extracellular matrix (ECM) networks enables cells to assemble a topological description of the chemical and mechanical properties of their surroundings. This information is then converted into intracellular signals that influence cell positioning, differentiation and growth, but may also influence other fundamental processes, such as protein synthesis and energy regulation...
September 5, 2018: Current Opinion in Cell Biology
Thomas J Humphries, Prasad Mathew
OBJECTIVE: The term cerebral microbleed (CMB) refers to lesions documented as unexpected findings during computed tomography or magnetic resonance imaging examination of the brain. Initially, a CMB was thought to represent hemosiderin-laden macrophages marking an area of a tiny hemorrhage. Recently, histopathologic studies have shown that the structure of a CMB can be variable. To aid in dealing with this finding and judging its clinical significance, this review addresses important aspects of a CMB including the definition, prevalence and incidence in various populations, end-organ damage, associated conditions, and whether any action or treatment by the clinician might be indicated...
September 7, 2018: Current Medical Research and Opinion
Zsolt Stockinger, Daniel Grabo, Avi Benov, Homer Tien, Jason Seery, Ashley Humphries
Unlike penetrating abdominal injuries where the decision to operate is relatively straight forward, those combat casualties that sustain blunt abdominal trauma offer more of a diagnostic and clinical challenge. For unstable patients with a positive focused abdominal sonography in trauma or diagnostic peritoneal lavage, exploratory laparotomy should be undertaken immediately. All grade IV-V splenic injuries should undergo splenectomy, patients undergoing attempted splenic salvage should be monitored in the Role 3 facility and embolization of such splenic injuries may be considered if available...
September 1, 2018: Military Medicine
Rebecca Y Linfield, Shelley Campeau, Patil Injean, Aric Gregson, Fady Kaldas, Zachary Rubin, Tae Kim, Danielle Kunz, Alfred Chan, Delphine J Lee, Romney M Humphries, James A McKinnell
OBJECTIVE: We evaluated the utility of vancomycin-resistant Enterococcus (VRE) surveillance by varying 2 parameters: admission versus weekly surveillance and perirectal swabbing versus stool sampling. DESIGN: Prospective, patient-level surveillance program of incident VRE colonization. SETTING: Liver transplant surgical intensive care unit (SICU) of a tertiary-care referral medical center with a high prevalence of VRE.PatientsAll patients admitted to the SICU from June to August 2015...
October 2018: Infection Control and Hospital Epidemiology
S Humphry, D Thompson, N Price, P R Williams
Aims: The significance of the 'clicky hip' in neonatal and infant examination remains controversial with recent conflicting papers reigniting the debate. We aimed to quantify rates of developmental dysplasia of the hip (DDH) in babies referred with 'clicky hips' to our dedicated DDH clinic. Patients and Methods: A three-year prospective cohort study was undertaken between 2014 and 2016 assessing the diagnosis and treatment outcomes of all children referred specifically with 'clicky hips' as the primary reason for referral to our dedicated DDH clinic...
September 2018: Bone & Joint Journal
Annie Vu, Tyler Humphries, Sean Vogel, Adam Haberman
Expansions of polygutamine-encoding stretches in several genes cause neurodegenerative disorders including Huntington's Disease and Spinocerebellar Ataxia type 3. Expression of the human disease alleles in Drosophila melanogaster neurons recapitulates cellular features of these disorders, and has therefore been used to model the cell biology of these diseases. Here, we show that polyglutamine disease alleles expressed in Drosophila photoreceptors disrupt actin structure at rhabdomeres, as other groups have shown they do in Drosophila and mammalian dendrites...
August 24, 2018: Molecular and Cellular Neurosciences
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