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UCL University College London Eprints (361,708 recursos)
UCL Eprints collects the work of UCL researchers and makes it freely available over the web, helping the worldwide scholarly community to discover UCL research. Institutional repositories like UCL Eprints complement the traditional academic publishing and scholarly communications processes. They raise the visibility of research and help to maximise its impact. UCL researchers are encouraged to deposit a copy of each journal article, conference paper, working paper, and any other research output, in the UCL Eprints at the earliest opportunity, ensuring that their research reaches as wide an audience as possible.

Mostrando recursos 1 - 20 de 365,626

1. Binocular Visual Responses in the Primate Lateral Geniculate Nucleus. - Zeater, N; Cheong, SK; Solomon, SG; Dreher, B; Martin, PR
The dorsal lateral geniculate nucleus (dLGN) in carnivores and primates is a laminated structure, where each layer gets visual input from only one eye [1, 2]. By contrast, in rodents such as mice and rats, the dLGN is not overtly laminated, the retinal terminals from the two eyes are only partially segregated [3, 4], and many cells in the binocular segment of dLGN get excitatory inputs from both eyes [5, 6]. Here, we show that the evolutionary ancient koniocellular (K) division of primate dLGN, like rodent dLGN, forms a subcortical site of binocular integration. We recorded single-cell activity in dLGN...

2. Changes in physical activity during transition to retirement: a cohort study. - Stenholm, S; Pulakka, A; Kawachi, I; Oksanen, T; Halonen, JI; Aalto, V; Kivimäki, M; Vahtera, J
BACKGROUND: Retirement is a major life transition which may affect lifestyle. The aim of this study is to examine within-individual changes in physical activity during the transition from full-time work to retirement. METHODS: The study population consisted of 9,488 Finnish public-sector employees who retired in 2000-2011 and who reported their leisure-time and commuting physical activity before and after retirement. On average, participants provided data at 3.6 (of the four) repeat examinations during 10 years before and 10 years after the retirement. Physical activity was self-reported and was expressed as weekly metabolic equivalent task (MET) hours. Generalized estimating equations were used to examine...

3. Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer. - Birge, RB; Boeltz, S; Kumar, S; Carlson, J; Wanderley, J; Calianese, D; Barcinski, M; Brekken, RA; Huang, X; Hutchins, JT; Freimark, B; Empig, C; Mercer, J; Schroit, AJ; Schett, G; Herrmann, M
Apoptosis is an evolutionarily conserved and tightly regulated cell death modality. It serves important roles in physiology by sculpting complex tissues during embryogenesis and by removing effete cells that have reached advanced age or whose genomes have been irreparably damaged. Apoptosis culminates in the rapid and decisive removal of cell corpses by efferocytosis, a term used to distinguish the engulfment of apoptotic cells from other phagocytic processes. Over the past decades, the molecular and cell biological events associated with efferocytosis have been rigorously studied, and many eat-me signals and receptors have been identified. The externalization of phosphatidylserine (PS) is arguably...

4. The incretin hormone glucagon-like peptide 1 increases mitral cell excitability by decreasing conductance of a voltage-dependent potassium channel. - Thiebaud, N; Llewellyn-Smith, IJ; Gribble, F; Reimann, F; Trapp, S; Fadool, DA
The olfactory system is intricately linked with the endocrine system where it may serve as a detector of internal metabolic state or energy homeostasis in addition to its classical function as a sensor of external olfactory information. The recent development of transgenic mGLU-YFP mice that express a genetic reporter under the control of the preproglucagon reporter, suggested the presence of the gut hormone, glucagon-like peptide (GLP-1) in deep short axon cells (dSAC; Cajal cells) of the olfactory bulb and its neuromodulatory effect on the mitral cell (MC) first order neurons. A MC target for the peptide was determined using GLP-1R...

5. Alzheimer's disease. - Scheltens, P; Blennow, K; Breteler, MM; de Strooper, B; Frisoni, GB; Salloway, S; Van der Flier, WM
Although the prevalence of dementia continues to increase worldwide, incidence in the western world might have decreased as a result of better vascular care and improved brain health. Alzheimer's disease, the most prevalent cause of dementia, is still defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality as proposed in the original amyloid hypothesis. Age-related, protective, and disease-promoting factors probably interact with the core mechanisms of the disease. Amyloid β42, and tau proteins are established core cerebrospinal biomarkers; novel candidate biomarkers include amyloid β oligomers and synaptic...

6. Hypothermic Preconditioning Reverses Tau Ontogenesis in Human Cortical Neurons and is Mimicked by Protein Phosphatase 2A Inhibition. - Rzechorzek, NM; Connick, P; Livesey, MR; Borooah, S; Patani, R; Burr, K; Story, D; Wyllie, DJ; Hardingham, GE; Chandran, S
Hypothermia is potently neuroprotective, but the molecular basis of this effect remains obscure. Changes in neuronal tau protein are of interest, since tau becomes hyperphosphorylated in injury-resistant, hypothermic brains. Noting inter-species differences in tau isoforms, we have used functional cortical neurons differentiated from human pluripotent stem cells (hCNs) to interrogate tau modulation during hypothermic preconditioning at clinically-relevant temperatures. Key tau developmental transitions (phosphorylation status and splicing shift) are recapitulated during hCN differentiation and subsequently reversed by mild (32 °C) to moderate (28 °C) cooling - conditions which reduce oxidative and excitotoxic stress-mediated injury in hCNs. Blocking a major tau kinase decreases hCN...

7. Seeking support after hospitalisation for injury: a nested qualitative study of the role of primary care. - Christie, N; Beckett, K; Earthy, S; Kellezi, B; Sleney, J; Barnes, J; Jones, T; Kendrick, D
BACKGROUND: In the UK, studies suggest that the transition from hospital to home after an injury can be a difficult time and many patients report feeling inadequately prepared. Patients often use primary care services after hospital discharge. These consultations provide opportunities to consider problems that patients experience and to facilitate recovery. Little is known, however, about how patients and service providers view care after hospital discharge and the role played by primary care services, specifically GPs. AIM: To identify good practice and unmet needs in respect of post-discharge support for injured patients. DESIGN AND SETTING: Qualitative study using semi-structured interviews...

8. Deactivating Cochlear Implant Electrodes Based on Pitch Information for Users of the ACE Strategy. - Vickers, D; Degun, A; Canas, A; Stainsby, T; Vanpoucke, F
There is a wide range in performance for cochlear implant (CI) users and there is some evidence to suggest that implant fitting can be modified to improve performance if electrodes that do not provide distinct pitch information are de-activated. However, improvements in performance may not be the same for users of all CI devices; in particular for those with Cochlear devices using n-of-m strategies (ACE or SPEAK).The goal of this research was to determine for users of Cochlear devices (CP810 or CP900 series processors) if speech perception could be improved when indiscriminable electrodes were de-activated and this was also compared...

9. Effect of hairpin loop structure on reactivity, sequence preference and adduct orientation of a DNA-interactive pyrrolo[2,1-c][1,4]benzodiazepine (PBD) antitumour agent. - Thurston, DE; Vassoler, H; Jackson, PJ; James, CH; Rahman, KM
The pyrrolobenzodiazepines (PBDs) are a family of covalent-binding DNA-interactive minor-groove binding agents with a thermodynamic preference for binding to 5'-Pu-G-Pu-3' sequences (Pu = Purine) but a kinetic preference for 5'-Py-G-Py-3' (Py = Pyrimidine). Using HPLC/MS methodology and a range of designed hairpin-forming oligonucleotides, the kinetics of reaction of a C8-bis-pyrrole pyrrolobenzodiazepine (PBD) conjugate (GWL-78, 2) with sixteen isomeric oligonucleotides has been evaluated, each containing a single PBD binding site in one of two locations. The PBD-binding base-pair triplets were designed to include every possible combination of A and T bases adjacent to the covalently-reacting guanine, with the set of hairpins...

10. Perioperative management of diabetes and the emerging role of anaesthetists as perioperative physicians. - Levy, N; Penfold, N; Mythen, M

11. Acute and Chronic Ophthalmic Involvement in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis - A Comprehensive Review and Guide to Therapy. II. Ophthalmic Disease. - Kohanim, S; Palioura, S; Saeed, HN; Akpek, EK; Amescua, G; Basu, S; Blomquist, PH; Bouchard, CS; Dart, JK; Gai, X; Gomes, JA; Gregory, DG; Iyer, G; Jacobs, DS; Johnson, AJ; Kinoshita, S; Mantagos, IS; Mehta, JS; Perez, VL; Pflugfelder, SC; Sangwan, VS; Sippel, KC; Sotozono, C; Srinivasan, B; Tan, DT; Tandon, R; Tseng, SC; Ueta, M; Chodosh, J
Our purpose is to comprehensively review the state of the art with regard to Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to improving the management of associated ocular surface complications. SJS and TEN are two ends of a spectrum of immune-mediated disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. Part I of this review focused on the systemic aspects of SJS/TEN and was published in the January 2016 issue of this journal. The purpose of Part II is to summarize the ocular manifestations and...

12. Bioaerosol production by patients with tuberculosis during normal tidal breathing: implications for transmission risk. - Wurie, FB; Lawn, SD; Booth, H; Sonnenberg, P; Hayward, AC
BACKGROUND: The size and concentration of exhaled bioaerosols may influence TB transmission risk. This study piloted bioaerosol measurement in patients with TB and assessed variability in bioaerosol production during normal tidal breathing. Understanding this may provide a tool for assessing heterogeneity in infectivity and may inform mathematical models of TB control practices and policies. METHODS: Optical particle counter technology was used to measure aerosol size and concentration in exhaled air (range 0.3-20 µm in diameter) during 15 tidal breaths across four groups over time: healthy/uninfected, healthy/Mycobacterium tuberculosis-infected, patients with extrathoracic TB and patients with intrathoracic TB. High-particle production was defined as...

13. Multivariable model development and internal validation for prostate cancer specific survival and overall survival after whole-gland salvage Iodine-125 prostate brachytherapy. - Peters, M; van der Voort van Zyp, JR; Moerland, MA; Hoekstra, CJ; van de Pol, S; Westendorp, H; Maenhout, M; Kattevilder, R; Verkooijen, HM; van Rossum, PS; Ahmed, HU; Shah, TT; Emberton, M; van Vulpen, M
BACKGROUND: Whole-gland salvage Iodine-125-brachytherapy is a potentially curative treatment strategy for localised prostate cancer (PCa) recurrences after radiotherapy. Prognostic factors influencing PCa-specific and overall survival (PCaSS & OS) are not known. The objective of this study was to develop a multivariable, internally validated prognostic model for survival after whole-gland salvage I-125-brachytherapy. MATERIALS AND METHODS: Whole-gland salvage I-125-brachytherapy patients treated in the Netherlands from 1993-2010 were included. Eligible patients had a transrectal ultrasound-guided biopsy-confirmed localised recurrence after biochemical failure (clinical judgement, ASTRO or Phoenix-definition). Recurrences were assessed clinically and with CT and/or MRI. Metastases were excluded using CT/MRI and technetium-99m scintigraphy....

14. Role of aetiology in the progression, regression, and parenchymal remodelling of liver disease implications for liver biopsy interpretation. - Quaglia, A; Alves, V; Balabaud, C; Bhathal, PS; Bioulac-Sage, P; Crawford, JM; Dhillon, AP; Ferrell, L; Guido, M; Hytiroglou, P; Nakanuma, Y; Paradis, V; Snover, DC; Theise, ND; Thung, SN; Tsui, WM; van Leeuwen, DJ
Clinicopathological concepts on acute and chronic liver disease have rapidly evolved over the last few years, with advances in general and specific treatment options, and improved patient outcomes. The old paradigm of "irreversibility" of cirrhosis had been challenged in major ways, and the validity of the usage of the term "cirrhosis" has come into question. This paper addresses aetiology-based clinicopathological concepts and features that may deserve attention because they may determine disease outcome and specifically patterns of regression and remodelling. A variety of therapeutic interventions may influence remaining disease features after elimination of damaging agents (virus, alcohol etc.), and determine...

15. A Longitudinal Analysis of Outcomes of Lupus Nephritis in an International Inception Cohort Using a Multistate Model Approach. - Hanly, JG; Su, L; Urowitz, MB; Romero-Diaz, J; Gordon, C; Bae, SC; Bernatsky, S; Clarke, AE; Wallace, DJ; Merrill, JT; Isenberg, DA; Rahman, A; Ginzler, EM; Petri, M; Bruce, IN; Dooley, MA; Fortin, P; Gladman, DD; Sanchez-Guerrero, J; Steinsson, K; Ramsey-Goldman, R; Khamashta, MA; Aranow, C; Alarcón, GS; Fessler, BJ; Manzi, S; Nived, O; Sturfelt, GK; Zoma, AA; van Vollenhoven, RF; Ramos-Casals, M; Ruiz-Irastorza, G; Sam Lim, S; Kalunian, KC; Inanc, M; Kamen, DL; Peschken, CA; Jacobsen, S; Askanase, A; Theriault, C; Farewell, V
OBJECTIVE: To study bidirectional change and predictors of change in estimated glomerular filtration rate (eGFR) and proteinuria (ePrU) in lupus nephritis (LN) using a multistate modelling approach. METHODS: In the SLICC inception cohort we determined annual eGFR state 1 (eGFR: >60 ml/min), 2 (eGFR: 30-60 mL/min), and 3 (eGFR: <30 ml/min); ePrU state 1 (ePrU: <0.25 gr/day), 2 (ePrU: 0.25-3.0 gr/day), and 3 (ePrU: >3.0 gr/day); End stage renal disease (ESRD) and death. Using multistate modelling, relative transition rates between states indicated improvement and deterioration. RESULTS: In 700/1,826 (38.3%) patients with LN, and mean (SD followup 5.2(3.5) years the likelihood...

16. Two Phase 2 Multiple Ascending-Dose Studies of Vanutide Cridificar (ACC-001) and QS-21 Adjuvant in Mild-to-Moderate Alzheimer's Disease. - Pasquier, F; Sadowsky, C; Holstein, A; Leterme, GL; Peng, Y; Jackson, N; Fox, NC; Ketter, N; Liu, E; Ryan, JM; ACC-001 (QS-21) Study Team,
Vanutide cridificar (ACC-001), an immunotherapeutic vaccine, is a potentially disease-modifying therapy that aims to reduce brain amyloid-β (Aβ) plaques in patients with Alzheimer's disease (AD). ACC-001 was evaluated in two phase 2a, multicenter, randomized, third party-unblinded, placebo-controlled, multiple ascending-dose studies of ACC-001 (3μg, 10μg, 30μg) with and without QS-21 adjuvant that enrolled patients with mild-to-moderate AD (n = 245). Patients were treated with up to five doses of study vaccine or placebo and followed for safety and tolerability (primary objective) and anti-Aβ IgG immunogenicity (secondary objective) up to 12 months after the last vaccination. Exploratory assessments included cognitive/functional measures, brain magnetic resonance...

17. Brief Report: Severe Inflammation Following Vaccination Against Streptococcus pneumoniae in Patients With Cryopyrin-Associated Periodic Syndromes. - Walker, UA; Hoffman, HM; Williams, R; Kuemmerle-Deschner, J; Hawkins, PN
OBJECTIVE: Pneumococcal vaccination is recommended for patients receiving immunosuppressive drugs. We describe unusually severe adverse reactions to pneumococcal vaccination in each of 7 consecutive patients with cryopyrin-associated periodic syndromes (CAPS). METHODS: Seven consecutive patients with CAPS were vaccinated with pneumococcal polysaccharide or conjugate vaccines. Clinical information was collected retrospectively. RESULTS: Within a few hours after the vaccination, all 7 patients developed severe local reactions at the injection site. Two patients had to be hospitalized for systemic reactions including fever. All symptoms resolved in a period of 3-17 days. CONCLUSION: Our findings indicate that pneumococcal vaccines can trigger a severe local...

18. Managing neurogenic bowel dysfunction: what do patients prefer? A discrete choice experiment of patient preferences for transanal irrigation and standard bowel management. - Nafees, B; Lloyd, AJ; Ballinger, RS; Emmanuel, A
BACKGROUND: Most patients with bowel dysfunction secondary to neurological illness are managed by a range of nonsurgical methods, including dietary changes, laxatives, and suppository use to transanal irrigation (TAI). The aim of the present study was to explore individuals' preferences regarding TAI devices and furthermore investigate willingness to pay (WTP) for attributes in devices in the UK. METHODS: A discrete choice experiment survey was conducted to evaluate the patients' perceived value of TAI devices. Attributes were selected based upon a literature review and input from clinicians. Interviews were conducted with three clinicians and the survey was developed and finalized with...

19. Interrelations between cognitive dysfunction and motor symptoms of Parkinson's disease: behavioral and neural studies. - Moustafa, AA; Chakravarthy, S; Phillips, JR; Crouse, JJ; Gupta, A; Frank, MJ; Hall, JM; Jahanshahi, M
Parkinson's disease (PD) is characterized by a range of motor symptoms. Besides the cardinal symptoms (tremor, bradykinesia/akinesia, and rigidity), PD patients also show other motor deficits, including gait disturbance, speech deficits, and impaired handwriting. However, along with these key motor symptoms, PD patients also experience cognitive deficits in attention, executive function, working memory, and learning. Recent evidence suggests that these motor and cognitive deficits of PD are not completely dissociable, as aspects of cognitive dysfunction can impact motor performance in PD. In this article, we provide a review of behavioral and neural studies on the associations between motor symptoms and...

20. Opposing Role of Tumor Necrosis Factor Receptor 1 Signaling in T Cell Mediated Hepatitis and Bacterial Infection In Mice. - Wroblewski, R; Armaka, M; Kondylis, V; Pasparakis, M; Walczak, H; Mittrücker, HW; Schramm, C; Lohse, AW; Kollias, G; Hanno, E
Death receptor (DR) ligands such as tumor necrosis factor (TNF) have been identified as fundamental mediators of liver damage both in mouse models and in humans. While the essential site of function of DR signaling is conceivably the hepatocyte, a systematic analysis is missing. Using mice with conditional gene ablation we analyzed the tissue-specific function of DR signaling in T cell-dependent (Concanavalin A, ConA) and independent (Lipopolysaccharide/Galactosamine, LPS/Gal) hepatitis and in models of bacterial infection (Listeria monocytogenes, LPS). We report that LPS/Gal-induced liver injury depends on hepatocyte-intrinsic TNF receptor 1 (p55, TNFR1). In contrast, we show that T cell-induced hepatitis...

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