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Keith Poole

Juliana B Lewis, Frank A Scangarello, Joanne M Murphy, Keith P Eidell, Michelle O Sodipo, Michael J Ophir, Ryan Sargeant, Maria-Cristina Seminario, Stephen C Bunnell
Antigen recognition by the T cell receptor (TCR) directs the assembly of essential signaling complexes known as SLP-76 microclusters. Here, we show that the interaction of the adhesion and degranulation-promoting adaptor protein (ADAP) with SLP-76 enables the formation of persistent microclusters and the stabilization of T cell contacts, promotes integrin-independent adhesion, and enables the upregulation of CD69. Using point mutants and a novel phospho-specific antibody, we show that Y595 is essential for normal ADAP function, that virtually all tyrosine phosphorylation of ADAP is restricted to a Y595-phosphorylated pool, and that multivalent interactions between the SLP-76 SH2 domain and its binding sites in ADAP are required to sustain ADAP phosphorylation...
October 10, 2018: Journal of Cell Science
Michael Fruci, Keith Poole
Exposure of P. aeruginosa to the aminoglycoside (AG) paromomycin (PAR) induced expression of the PA3720-armR locus and the mexAB-oprM multidrug efflux operon that AmgR controls, although PAR induction of mexAB-oprM was independent of armR. Multiple AGs promoted mexAB-oprM expression and this was lost in the absence of the amgRS locus encoding an aminoglycoside-activated envelope stress-responsive 2-component system (TCS). Purified AmgR bound to the mexAB-oprM promoter region consistent with this response regulator directly regulating expression of the efflux operon...
2018: PloS One
Nina M A Frampton, Julia C Poole, Keith S Dobson, Dennis Pusch
Adverse childhood experiences (ACEs) have been linked to numerous negative physical and mental health outcomes across the lifespan. As such, self-report questionnaires that assess for ACEs are increasingly used in healthcare settings. However, previous research has generated some concern over the reliability of retrospective reports of childhood adversity, and it has been proposed that symptoms of depression may increase recall of negative memories. To investigate the stability of ACE scores over time and whether they are influenced by symptoms of depression, we recruited 284 participants (M age = 40...
September 26, 2018: Child Abuse & Neglect
Luis San Román, Bijoy K Menon, Jordi Blasco, María Hernández-Pérez, Antoni Dávalos, Charles B L M Majoie, Bruce C V Campbell, Francis Guillemin, Hester Lingsma, René Anxionnat, Jonathan Epstein, Jeffrey L Saver, Henk Marquering, John H Wong, Demetrius Lopes, Gernot Reimann, Hubert Desal, Diederik W J Dippel, Shelagh Coutts, Richard du Mesnil de Rochemont, Dileep Yavagal, Jean Christophe Ferre, Yvo B W E M Roos, David S Liebeskind, Robert Lenthall, Carlos Molina, Fahad S Al Ajlan, Vivek Reddy, Dar Dowlatshahi, Sourour Nader-Antoine, Catherine Oppenheim, Alim P Mitha, Stephen M Davis, Christian Weimar, Robert J van Oostenbrugge, Erik Cobo, Timothy J Kleinig, Geoffrey A Donnan, Aad van der Lugt, Andrew M Demchuk, Olvert A Berkhemer, Anna M M Boers, Gary A Ford, Keith W Muir, B Scott Brown, Tudor Jovin, Wim H van Zwam, Peter J Mitchell, Michael D Hill, Phil White, Serge Bracard, Mayank Goyal
BACKGROUND: Evidence regarding whether imaging can be used effectively to select patients for endovascular thrombectomy (EVT) is scarce. We aimed to investigate the association between baseline imaging features and safety and efficacy of EVT in acute ischaemic stroke caused by anterior large-vessel occlusion. METHODS: In this meta-analysis of individual patient-level data, the HERMES collaboration identified in PubMed seven randomised trials in endovascular stroke that compared EVT with standard medical therapy, published between Jan 1, 2010, and Oct 31, 2017...
October 2018: Lancet Neurology
Keith C Ferdinand, George L Bakris, William C Cushman, Michael A Weber, Eric Lloyd, Jingtao Wu, William B White
Two post hoc analyses in self-identified black and white patients with hypertension evaluated the angiotensin II receptor blocker azilsartan medoxomil (AZL-M) and the fixed-dose combination of AZL-M with chlorthalidone (AZL-M/CLD) versus the ARB olmesartan (OLM) and the OLM fixed-dose combination with hydrochlorothiazide (OLM/HCTZ). One analysis pooled 1,610 patients from two 6-week randomized controlled trials to compare once daily AZL-M 40mg, AZL-M 80mg, OLM 40mg, and placebo. The second analysis included 1,020 patients from a 12-week randomized controlled trial to compare once daily AZL-M/CLD 40/25mg, AZL-M/CLD 80/25mg, and OLM/HCTZ 40/25mg...
August 4, 2018: American Journal of Cardiology
George H Searfoss, Brianna M Paisley, Keith M Goldstein, Thomas K Baker, Jeffrey A Willy
The discovery of mammalian cardiac progenitor cells has suggested that the heart consists of not only terminally differentiated beating cardiomyocytes, but also a population of self-renewing stem cells with the potential to generate new cardiomyocytes (Anderson, Self et al. 2007; Bearzi, Rota et al. 2007; Wu, Chien et al. 2008). A consequence of longevity is continual exposure to environmental and xenobiotic stresses, and recent literature suggests that hematopoietic stem cell pools tightly control cell health through upregulation of the integrated stress response and consequent cellular mechanisms such as apoptosis...
September 12, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Ian D Cameron, Suzanne M Dyer, Claire E Panagoda, Geoffrey R Murray, Keith D Hill, Robert G Cumming, Ngaire Kerse
BACKGROUND: Falls in care facilities and hospitals are common events that cause considerable morbidity and mortality for older people. This is an update of a review first published in 2010 and updated in 2012. OBJECTIVES: To assess the effects of interventions designed to reduce the incidence of falls in older people in care facilities and hospitals. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (August 2017); Cochrane Central Register of Controlled Trials (2017, Issue 8); and MEDLINE, Embase, CINAHL and trial registers to August 2017...
September 7, 2018: Cochrane Database of Systematic Reviews
Drake G LeBrun, Bibek Banskota, Ashok K Banskota, Tarun Rajbhandari, Keith D Baldwin, David A Spiegel
BACKGROUND: Cerebral palsy (CP) comprises a heterogeneous group of disorders whose clinical manifestations and epidemiologic characteristics vary across socioeconomic and geographic contexts. The functional severity of untreated CP in low-income countries has been insufficiently studied; a better understanding of how these children present for care in resource-constrained environments is important because it will better characterize the natural history of CP, guide clinical decision-making, and aid in the prognostication of children with untreated CP...
August 30, 2018: Clinical Orthopaedics and related Research
Francesca Ferraro, Feng Gao, Keith Stockerl-Goldstein, Peter Westervelt, John F DiPersio, Armin Ghobadi
Secondary acute lymphoblastic leukemia (s-ALL) is rare and poorly defined and data regarding outcomes post-transplant are lacking. Here, we report a detailed analysis of s-ALL at our Institution. Among 211 eligible patients with ALL from 2006 to 2017, 30 (14%) were defined as s-ALL and the remaining as primary ALL (p-ALL). s-ALL patients were older and had higher incidence of adverse risk factors. Overall response (OR) after induction was not different between s-ALL and p-ALL (79% versus 90% respectively, p = 0...
September 2018: Leukemia Research
Sarah Stewart, Angela Brenton-Rule, Nicola Dalbeth, Ashok Aiyer, Christopher Frampton, Keith Rome
OBJECTIVE: To determine characteristics of the foot and ankle in people with systemic lupus erythematosus (SLE). METHODS: Medline, CINAHL, Sports-Discus, Scopus and Cochrane Library databases were searched up to January 2018. Studies reporting foot- and ankle-related outcomes in the following domains were included: vascular, neurological, musculoskeletal, cutaneous (skin and nail) or pain/function. The Quality Index tool was used to assess methodological quality...
August 6, 2018: Seminars in Arthritis and Rheumatism
Axel Hauschild, James Larkin, Antoni Ribas, Brigitte Dréno, Keith T Flaherty, Paolo A Ascierto, Karl D Lewis, Edward McKenna, Qian Zhu, Yong Mun, Grant A McArthur
Importance: Prognostic models may provide insight into clinical trial results and inform the clinical management of patients with BRAF V600-mutated metastatic melanoma. Objective: To identify subgroups with distinct survival outcomes based on clinical and genomic characteristics and to assess survival in identified prognostic subgroups across cohorts treated with dacarbazine, vemurafenib, or cobimetinib plus vemurafenib. Design, Setting, and Participants: This retrospective and exploratory recursive partitioning analysis (RPA) modeled associations between prespecified covariates and survival outcomes using pooled data from the BRIM-2, BRIM-3, BRIM-7, and coBRIM studies...
October 1, 2018: JAMA Oncology
Courtland S Hyatt, Chelsea E Sleep, Joanna Lamkin, Jessica L Maples-Keller, Constantine Sedikides, W Keith Campbell, Joshua D Miller
Similarity between narcissism and self-esteem seems intuitive, as both capture positive perceptions of the self. In the current undertaking, we provide a broad comparison of the nomological networks of grandiose narcissism and explicit self-esteem. Pooling data from 11 existing samples (N = 4711), we compared the relations of narcissism and self-esteem to developmental experiences, individual differences, interpersonal functioning, and psychopathology. Both constructs are positively related to agentic traits and assertive interpersonal approaches, but differ in relation to agreeableness/communion...
2018: PloS One
Keith R Martin, Kaweh Mansouri, Robert N Weinreb, Robert Wasilewicz, Christophe Gisler, Jean Hennebert, Dominique Genoud
PURPOSE: To test the hypothesis that contact lens sensor (CLS)-based 24-hour profiles of ocular volume changes contain information complementary to intraocular pressure (IOP) to discriminate between primary open-angle glaucoma (POAG) and healthy (H) eyes. DESIGN: Development and evaluation of a diagnostic test with machine learning. METHODS: Subjects: From 435 subjects (193 healthy and 242 POAG), 136 POAG and 136 age-matched healthy subjects were selected...
October 2018: American Journal of Ophthalmology
Yuxin Liu, Keith Sigel, Michael M Gaisa
Background: High-risk human papillomavirus (hrHPV)-induced anal low-grade squamous intraepithelial lesions (LSIL) have the potential to progress to high-grade SIL (HSIL). We investigated whether anal hrHPV infections, particularly types 16 and 18, predict LSIL-to-HSIL progression. Methods: 146 HIV-infected and 22 HIV-uninfected patients with anal LSIL underwent cytology, HPV genotyping (16, 18, and pooled 12 hrHPV), and high-resolution anoscopy-guided biopsy at baseline and surveillance...
July 21, 2018: Journal of Infectious Diseases
Álvaro H Borges, Jacqueline Neuhaus, Shweta Sharma, James D Neaton, Keith Henry, Olga Anagnostou, Teresa Staub, Sean Emery, Jens D Lundgren
Background: Pooled data from SMART and START were used to compare deferred/intermittent versus immediate/continuous antiretroviral therapy (ART) on disease risk. Methods: Endpoints assessed were AIDS, serious non-AIDS (SNA), cardiovascular disease (CVD), cancer, and death. Pooled (stratified by study) hazard ratios (HRs) from Cox models were obtained for deferred/intermittent ART vs immediate/continuous ART; analyses were conducted to assess consistency of HRs across baseline-defined subgroups...
July 19, 2018: Journal of Infectious Diseases
Keith R Laws, Nicole Darlington, Tejinder K Kondel, Peter J McKenna, Sameer Jauhar
BACKGROUND: The effect of cognitive behavioural therapy for psychosis (CBTp) on the core symptoms of schizophrenia has proven contentious, with current meta-analyses finding at most only small effects. However, it has been suggested that the effects of CBTp in areas other than psychotic symptoms are at least as important and potentially benefit from the intervention. METHOD: We meta-analysed RCTs investigating the effectiveness of CBTp for functioning, distress and quality of life in individuals diagnosed with schizophrenia and related disorders...
July 17, 2018: BMC Psychology
Dipti Pawaskar, Michael A Tortorici, Bruce Zuraw, Timothy Craig, Marco Cicardi, Hilary Longhurst, H Henry Li, William R Lumry, Inmaculada Martinez-Saguer, Joshua Jacobs, Jonathan A Bernstein, Marc A Riedl, Constance H Katelaris, Paul K Keith, Annette Feussner, Jagdev Sidhu
BACKGROUND: Long-term prophylaxis with subcutaneous (SC) administration of a highly concentrated plasma-derived C1-esterase inhibitor (C1-INH) formulation was recently approved by the Food and Drug Administration for hereditary angioedema (HAE) attack prevention. OBJECTIVE: To characterize the population pharmacokinetics of C1-INH (SC) (HAEGARDA® ; CSL Behring) in healthy volunteers and HAE patients, and assess the variability and influence of covariates on pharmacokinetics...
October 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Michele Di Mascio, Sharat Srinivasula, Insook Kim, Gorka Duralde, Alexis St Claire, Paula DeGrange, Marisa St Claire, Keith A Reimann, Erin E Gabriel, Jorge Carrasquillo, Richard C Reba, Chang Paik, Henry C Lane
The peripheral blood represents only a small fraction of the total number of lymphocytes in the body. To develop a more thorough understanding of T cell dynamics, including the effects of SIV/SHIV/HIV infection on immune cell depletion and immune reconstitution following combination antiretroviral therapy (cART), one needs to utilize approaches that allow direct visualization of lymphoid tissues. In the present study, noninvasive in vivo imaging of the CD4+ T cell pool has revealed that the timing of the CD4+ T cell pool reconstitution following initiation of ART in SIV-infected nonhuman primates (NHPs) appears seemingly stochastic among clusters of lymph nodes within the same host...
July 12, 2018: JCI Insight
Ajai Chari, A Keith Stewart, Stuart D Russell, Philippe Moreau, Joerg Herrmann, Jose Banchs, Roman Hajek, John Groarke, Alexander R Lyon, George N Batty, Sunhee Ro, Mei Huang, Karim S Iskander, Daniel Lenihan
Carfilzomib is a selective proteasome inhibitor approved for the treatment of relapsed and/or refractory multiple myeloma (RRMM). It has significantly improved outcomes, including overall survival (OS), and shown superiority vs standard treatment with lenalidomide plus dexamethasone and bortezomib plus dexamethasone. The incidence rate of cardiovascular (CV) events with carfilzomib treatment has varied across trials. This analysis evaluated phase 1-3 trials with >2000 RRMM patients exposed to carfilzomib to describe the incidence of CV adverse events (AEs)...
July 10, 2018: Blood Advances
Nicholas R LaBonte, Peng Zhao, Keith Woeste
Chestnuts ( Castanea ) are major nut crops in East Asia and southern Europe, and are unique among temperate nut crops in that the harvested seeds are starchy rather than oily. Chestnut species have been cultivated for three millennia or more in China, so it is likely that artificial selection has affected the genome of orchard-grown chestnuts. The genetics of Chinese chestnut ( Castanea mollissima Blume) domestication are also of interest to breeders of hybrid American chestnut, especially if the low-growing, branching habit of Chinese chestnut, an impediment to American chestnut restoration, is partly the result of artificial selection...
2018: Frontiers in Plant Science
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