5,007 research outputs found
Typical and atypical presenting symptoms of breast cancer and their associations with diagnostic intervals: Evidence from a national audit of cancer diagnosis
This is the final published version. Available from Elsevier via the DOI in this record.Introduction Most symptomatic women with breast cancer have relatively short diagnostic intervals but a substantial minority experience prolonged journeys to diagnosis. Atypical presentations (with symptoms other than breast lump) may be responsible. Methods We examined the presenting symptoms of breast cancer in women using data from a national audit initiative (n = 2316). Symptoms were categorised topographically. We investigated variation in the length of the patient interval (time from symptom onset to presentation) and the primary care interval (time from presentation to specialist referral) across symptom groups using descriptive analyses and quantile regression. Results A total of 56 presenting symptoms were described: breast lump was the most frequent (83%) followed by non-lump breast symptoms, (e.g. nipple abnormalities (7%) and breast pain (6%)); and non-breast symptoms (e.g. back pain (1%) and weight loss (0.3%)). Greater proportions of women with ânon-lump onlyâ and âboth lump and non-lumpâ symptoms waited 90 days or longer before seeking help compared to those with âbreast lump onlyâ (15% and 20% vs. 7% respectively). Quantile regression indicated that the differences in the patient interval persisted after adjusting for age and ethnicity, but there was little variation in primary care interval for the majority of women. Conclusions About 1 in 6 women with breast cancer present with a large spectrum of symptoms other than breast lump. Women who present with non-lump breast symptoms tend to delay seeking help. Further emphasis of breast symptoms other than breast lump in symptom awareness campaigns is warranted.UK Department of HealthCancer Research U
Evaluating Maintainability Prejudices with a Large-Scale Study of Open-Source Projects
Exaggeration or context changes can render maintainability experience into
prejudice. For example, JavaScript is often seen as least elegant language and
hence of lowest maintainability. Such prejudice should not guide decisions
without prior empirical validation. We formulated 10 hypotheses about
maintainability based on prejudices and test them in a large set of open-source
projects (6,897 GitHub repositories, 402 million lines, 5 programming
languages). We operationalize maintainability with five static analysis
metrics. We found that JavaScript code is not worse than other code, Java code
shows higher maintainability than C# code and C code has longer methods than
other code. The quality of interface documentation is better in Java code than
in other code. Code developed by teams is not of higher and large code bases
not of lower maintainability. Projects with high maintainability are not more
popular or more often forked. Overall, most hypotheses are not supported by
open-source data.Comment: 20 page
Associations between diagnostic pathways and care experience in colorectal cancer: Evidence from patient-reported data
This is the final version. Available from the publisher via the DOI in this recordObjective: To examine how different pathways to diagnosis of colorectal cancer may be associated with the experience of subsequent care. Design: Patient survey linked to information on diagnostic route. English patients with colorectal cancer (analysis sample n=6837) who responded to a patient survey soon after their hospital treatment. Main outcome measures: Odds Ratios and adjusted proportions of negative evaluation of key aspects of care for colorectal cancer, including the experience of shared decision-making about treatment, specialist nursing and care coordination, by diagnostic route (ie, screening detection, emergency presentation, urgent and elective general practitioner referral). Results: For 14 of 18 questions, there was evidence (pâ¤0.02) for variation in patient experience by diagnostic route, with 6-31 percentage point differences between routes in adjusted proportions of negative experience. Emergency presenters were more likely to report a negative experience for most questions, including those about adequacy of information about their diagnosis and sufficient explanation before operations. Screen-detected patients were least likely to report negative experiences except for support from primary care. Patients diagnosed through elective primary care referrals were most likely to report worse experience for questions for which overall variation by route was generally small. Conclusions: Screening-detected patients tend to report the best and emergency presenters the worst experience of subsequent care. Improvement efforts can target care integration for screening-detected patients and provision of information about the diagnosis and treatment of emergency presenters.Cancer Research U
Finite temperature stability and dimensional crossover of exotic superfluidity in lattices
We investigate exotic paired states of spin-imbalanced Fermi gases in
anisotropic lattices, tuning the dimension between one and three. We calculate
the finite temperature phase diagram of the system using real-space dynamical
mean-field theory in combination with the quantum Monte Carlo method. We find
that regardless of the intermediate dimensions examined, the
Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) state survives to reach about one third
of the BCS critical temperature of the spin-density balanced case. We show how
the gapless nature of the state found is reflected in the local spectral
function. While the FFLO state is found at a wide range of polarizations at low
temperatures across the dimensional crossover, with increasing temperature we
find out strongly dimensionality-dependent melting characteristics of shell
structures related to harmonic confinement. Moreover, we show that intermediate
dimension can help to stabilize an extremely uniform finite temperature FFLO
state despite the presence of harmonic confinement.Comment: 5 pages, 3 figure
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Membrane Hsp70 â a novel target for the isolation of circulating tumor cells after epithelial-to-mesenchymal transition
The presence of circulating tumor cells (CTCs) in the peripheral blood is a pre-requisite for progression, invasion, and metastatic spread of cancer. Consequently, the enumeration and molecular characterization of CTCs from the peripheral blood of patients with solid tumors before, during and after treatment serves as a valuable tool for categorizing disease, evaluating prognosis and for predicting and monitoring therapeutic responsiveness. Many of the techniques for isolating CTCs are based on the expression of epithelial cell surface adhesion molecule (EpCAM, CD326) on tumor cells. However, the transition of adherent epithelial cells to migratory mesenchymal cells (epithelial-to-mesenchymal transition, EMT)âan essential element of the metastatic processâis frequently associated with a loss of expression of epithelial cell markers, including EpCAM. A highly relevant proportion of mesenchymal CTCs cannot therefore be isolated using techniques that are based on the âcaptureâ of cells expressing EpCAM. Herein, we provide evidence that a monoclonal antibody (mAb) directed against a membrane-bound form of Hsp70 (mHsp70)âcmHsp70.1âcan be used for the isolation of viable CTCs from peripheral blood of tumor patients of different entities in a more quantitative manner. In contrast to EpCAM, the expression of mHsp70 remains stably upregulated on migratory, mesenchymal CTCs, metastases and cells that have been triggered to undergo EMT. Therefore, we propose that approaches for isolating CTCs based on the capture of cells that express mHsp70 using the cmHsp70.1 mAb are superior to those based on EpCAM expression
Type 1 plasminogen activator inhibitor (PAI-1) in clear cell renal cell carcinoma (CCRCC) and its impact on angiogenesis, progression and patient survival after radical nephrectomy
<p>Abstract</p> <p>Background</p> <p>To examine the expression of type 1 plasminogen inhibitor (PAI-1) in clear cell renal cell carcinoma (CCRCC), and its possible association with microvessel density (MVD), the expression of thrombospondin-1 (TSP-1), nuclear grade, tumour stage, continuously coded tumour size (CCTS) and to assess the value of PAI as a prognostic marker in 162 patients with CCRCC treated with radical nephrectomy.</p> <p>Methods</p> <p>A total of 172 consecutive patients with CCRCC treated with radical nephrectomy were enrolled in the study. The expression of PAI-1, TSP-1 and factor VIII were analysed on formalin-fixed, paraffin-embedded tissues without knowledge of the clinical outcome. Ten cases, where PAI-1 immunohistochemistry was not possible due to technical problems and lack of material, were excluded. Sixty-nine patients (43%) died of RCC, while 47 patients (29%) died of other diseases. Median follow-up was 13.8 years for the surviving 46 patients (28%).</p> <p>Results</p> <p>Nine percent of the tumours showed PAI-1 positivity. High expression of PAI-1 was significantly inversely correlated with TSP-1 (p = 0.046) and directly with advanced stage (p = 0.008), high NG (3+4) (p = 0.002), tumour size (p = 0.011), microvessel density (p = 0.049) and disease progression (p = 0.002). In univariate analysis PAI-1 was a significant prognosticator of cancer-specific survival (CSS) (p < 0.001). Multivariate analysis revealed that TNM stage (p < 0.001), PAI-1 (p = 0.020), TSP-1 (p < 0.001) and MVD (p = 0.007) were independent predictors of CSS.</p> <p>Conclusions</p> <p>PAI-1 was found to be an independently significant prognosticator of CSS and a promoter of tumour angiogenesis, aggressiveness and progression in CCRCC.</p
Search algorithms as a framework for the optimization of drug combinations
Combination therapies are often needed for effective clinical outcomes in the
management of complex diseases, but presently they are generally based on
empirical clinical experience. Here we suggest a novel application of search
algorithms, originally developed for digital communication, modified to
optimize combinations of therapeutic interventions. In biological experiments
measuring the restoration of the decline with age in heart function and
exercise capacity in Drosophila melanogaster, we found that search algorithms
correctly identified optimal combinations of four drugs with only one third of
the tests performed in a fully factorial search. In experiments identifying
combinations of three doses of up to six drugs for selective killing of human
cancer cells, search algorithms resulted in a highly significant enrichment of
selective combinations compared with random searches. In simulations using a
network model of cell death, we found that the search algorithms identified the
optimal combinations of 6-9 interventions in 80-90% of tests, compared with
15-30% for an equivalent random search. These findings suggest that modified
search algorithms from information theory have the potential to enhance the
discovery of novel therapeutic drug combinations. This report also helps to
frame a biomedical problem that will benefit from an interdisciplinary effort
and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio
Religious Experience and the Modernist Novel
Output Type: Book Revie
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
Angiographic findings and clinical implications of persistent primitive hypoglossal artery
BACKGROUND: The primitive hypoglossal artery (PHA) is a rare vascular anomaly, which belongs to the group of carotid-basilar anastomosis that may occur in adults. CASE PRESENTATION: Herein is presented a case of a patient with a PHA, who had undergone a cerebral angiography due to investigation of subarachnoid hemorrhage. Additionally, the diagnostic alternatives for detection and assessment of PHA and the spectrum of diseases related to its presence are discussed. CONCLUSIONS: The presence of a persistent PHA can be recognized as an incidental finding in a cerebral angiography without any other clinical implication or may be associated with certain clinical entities such as aneurysm formation and atherosclerotic disease
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