1,562 research outputs found
Prognostic value of lymph node ratio and extramural vascular invasion on survival for patients undergoing curative colon cancer resection
There was no study funding. We are grateful to Tony Rafferty (Tailored Information for the People of Scotland, TIPs) for providing survival data.Peer reviewedPublisher PD
Redox linked flavin sites in extracellular decaheme proteins involved in microbe-mineral electron transfer
Extracellular microbe-mineral electron transfer is a major driving force for the oxidation of organic carbon in many subsurface environments. Extracellular multi-heme cytochromes of the Shewenella genus play a major role in this process but the mechanism of electron exchange at the interface between cytochrome and acceptor is widely debated. The 1.8 Å x-ray crystal structure of the decaheme MtrC revealed a highly conserved CX8C disulfide that, when substituted for AX8A, severely compromised the ability of S. oneidensis to grow under aerobic conditions. Reductive cleavage of the disulfide in the presence of flavin mononucleotide (FMN) resulted in the reversible formation of a stable flavocytochrome. Similar results were also observed with other decaheme cytochromes, OmcA, MtrF and UndA. The data suggest that these decaheme cytochromes can transition between highly reactive flavocytochromes or less reactive cytochromes, and that this transition is controlled by a redox active disulfide that responds to the presence of oxygen
Survey of the quality of experimental design, statistical analysis and reporting of research using animals
For scientific, ethical and economic reasons, experiments involving animals should be appropriately designed, correctly analysed and transparently reported. This increases the scientific validity of the results, and maximises the knowledge gained from each experiment. A minimum amount of relevant information must be included in scientific publications to ensure that the methods and results of a study can be reviewed, analysed and repeated. Omitting essential information can raise scientific and ethical concerns. We report the findings of a systematic survey of reporting, experimental design and statistical analysis in published biomedical research using laboratory animals. Medline and EMBASE were searched for studies reporting research on live rats, mice and non-human primates carried out in UK and US publicly funded research establishments. Detailed information was collected from 271 publications, about the objective or hypothesis of the study, the number, sex, age and/or weight of animals used, and experimental and statistical methods. Only 59% of the studies stated the hypothesis or objective of the study and the number and characteristics of the animals used. Appropriate and efficient experimental design is a critical component of high-quality science. Most of the papers surveyed did not use randomisation (87%) or blinding (86%), to reduce bias in animal selection and outcome assessment. Only 70% of the publications that used statistical methods described their methods and presented the results with a measure of error or variability. This survey has identified a number of issues that need to be addressed in order to improve experimental design and reporting in publications describing research using animals. Scientific publication is a powerful and important source of information; the authors of scientific publications therefore have a responsibility to describe their methods and results comprehensively, accurately and transparently, and peer reviewers and journal editors share the responsibility to ensure that published studies fulfil these criteria
Observations of X-ray Flares from Gamma Ray Bursts
Swift-XRT observations of the X-ray emission from gamma ray bursts (GRBs) and
during the GRB afterglow have led to many new results during the past two
years. One of these exciting results is that approximately 1/3-1/2 of GRBs
contain detectable X-ray flares. The mean fluence of the X-ray flares is ~10
times less than that of the initial prompt emission, but in some cases the
flare is as energetic as the prompt emission itself. The flares display fast
rises and decays, and they sometimes occur at very late times relative to the
prompt emission (sometimes as late as 10^5 s after T_0) with very high peak
fluxes relative to the underlying afterglow decay that has clearly begun prior
to some flares. The temporal and spectral properties of the flares are found to
favor models in which flares arise due to the same GRB internal engine
processes that spawned the prompt GRB emission. Therefore, both long and short
GRB internal engine models must be capable of producing high fluences in the
X-ray band at very late times.Comment: Solicited paper to appear in Proceedings of Gamma Ray Bursts 2007
Meeting, Santa Fe, New Mexico; 6 pages, 4 figure
LGR5 Activates Noncanonical Wnt Signaling and Inhibits Aldosterone Production in the Human Adrenal.
CONTEXT: Aldosterone synthesis and cellularity in the human adrenal zona glomerulosa (ZG) is sparse and patchy, presumably due to salt excess. The frequency of somatic mutations causing aldosterone-producing adenomas (APAs) may be a consequence of protection from cell loss by constitutive aldosterone production. OBJECTIVE: The objective of the study was to delineate a process in human ZG, which may regulate both aldosterone production and cell turnover. DESIGN: This study included a comparison of 20 pairs of ZG and zona fasciculata transcriptomes from adrenals adjacent to an APA (n = 13) or a pheochromocytoma (n = 7). INTERVENTIONS: Interventions included an overexpression of the top ZG gene (LGR5) or stimulation by its ligand (R-spondin-3). MAIN OUTCOME MEASURES: A transcriptome profile of ZG and zona fasciculata and aldosterone production, cell kinetic measurements, and Wnt signaling activity of LGR5 transfected or R-spondin-3-stimulated cells were measured. RESULTS: LGR5 was the top gene up-regulated in ZG (25-fold). The gene for its cognate ligand R-spondin-3, RSPO3, was 5-fold up-regulated. In total, 18 genes associated with the Wnt pathway were greater than 2-fold up-regulated. ZG selectivity of LGR5, and its absence in most APAs, were confirmed by quantitative PCR and immunohistochemistry. Both R-spondin-3 stimulation and LGR5 transfection of human adrenal cells suppressed aldosterone production. There was reduced proliferation and increased apoptosis of transfected cells, and the noncanonical activator protein-1/Jun pathway was stimulated more than the canonical Wnt pathway (3-fold vs 1.3-fold). ZG of adrenal sections stained positive for apoptosis markers. CONCLUSION: LGR5 is the most selectively expressed gene in human ZG and reduces aldosterone production and cell number. Such conditions may favor cells whose somatic mutation reverses aldosterone inhibition and cell loss.This work was supported by MJB is an NIHR Senior Investigator
NF-SI-0512–10 052; LHS holds a British Heart Foundation PhD studentship FS/11/35/28871; JZ holds a Cambridge Overseas Trust Scholarship; AEDT is funded by the Wellcome Trust Translational Medicine and Therapeutics program 085 686/Z/08/A, and by Singapore A* program; EABA was supported by the Austin Doyle Award (Servier Australia); LHS, JZ and EABA were additionally supported by the NIHR Cambridge Biomedical Research Centre; GM are funded by MRC Programme Grants RDAG/287 and SKAG/001 awarded to Ashok Venkitaraman.This is the author accepted manuscript. The final version is available from the Endocrine Society via http://dx.doi.org/10.1210/jc.2015-173
Patients with Asthma and Comorbid Allergic Rhinitis: Is Optimal Quality of Life Achievable in Real Life?
Asthma trials suggest that patients reaching total disease control have an optimal Health Related Quality of Life (HRQoL). Moreover, rhinitis is present in almost 80% of asthmatics and impacts asthma control and patient HRQoL. We explored whether optimal HRQoL was reachable in a real-life setting, and evaluated the disease and patient related patterns associated to optimal HRQoL achievement. = 7.617; p<0.006).Approximately one third of the patients in our survey were found to have an optimal HRQoL. While unsatisfactory disease control was the primary reason why the remainder failed to attain optimal HRQoL, it is clear that illness perception and mood also played parts. Therefore, therapeutic plans should be directed not only toward achieving the best possible clinical control of asthma and comorbid rhinitis, but also to incorporating individualized elements according to patient-related characteristics
Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease
Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures
A mathematical model for breath gas analysis of volatile organic compounds with special emphasis on acetone
Recommended standardized procedures for determining exhaled lower respiratory
nitric oxide and nasal nitric oxide have been developed by task forces of the
European Respiratory Society and the American Thoracic Society. These
recommendations have paved the way for the measurement of nitric oxide to
become a diagnostic tool for specific clinical applications. It would be
desirable to develop similar guidelines for the sampling of other trace gases
in exhaled breath, especially volatile organic compounds (VOCs) which reflect
ongoing metabolism. The concentrations of water-soluble, blood-borne substances
in exhaled breath are influenced by: (i) breathing patterns affecting gas
exchange in the conducting airways; (ii) the concentrations in the
tracheo-bronchial lining fluid; (iii) the alveolar and systemic concentrations
of the compound. The classical Farhi equation takes only the alveolar
concentrations into account. Real-time measurements of acetone in end-tidal
breath under an ergometer challenge show characteristics which cannot be
explained within the Farhi setting. Here we develop a compartment model that
reliably captures these profiles and is capable of relating breath to the
systemic concentrations of acetone. By comparison with experimental data it is
inferred that the major part of variability in breath acetone concentrations
(e.g., in response to moderate exercise or altered breathing patterns) can be
attributed to airway gas exchange, with minimal changes of the underlying blood
and tissue concentrations. Moreover, it is deduced that measured end-tidal
breath concentrations of acetone determined during resting conditions and free
breathing will be rather poor indicators for endogenous levels. Particularly,
the current formulation includes the classical Farhi and the Scheid series
inhomogeneity model as special limiting cases.Comment: 38 page
Experimental investigations of the sub-Coulomb 12C+12C and 12C+16O reactions
Cluster resonances in light heavy-ion systems like 12C+12C and 12C+16O may have a major impact on astrophysics stellar scenarios. Resonant radiative capture reactions have been studied for these systems at energies at and slightly below their Coulomb barriers to investigate the possible 12C-12C and 12C-16O molecular origin of the resonances. Spins have been attributed to the resonances and specificities of their γ-decay have been identified. At deep sub-barrier energies, a fusion cross section measurement using the particle-γ coincidence technique is discussed for the 12C+12C system. A new project is presented to possibly extend the 12C+12C S low-energy S factor study
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