180 research outputs found
Linear, Deterministic, and Order-Invariant Initialization Methods for the K-Means Clustering Algorithm
Over the past five decades, k-means has become the clustering algorithm of
choice in many application domains primarily due to its simplicity, time/space
efficiency, and invariance to the ordering of the data points. Unfortunately,
the algorithm's sensitivity to the initial selection of the cluster centers
remains to be its most serious drawback. Numerous initialization methods have
been proposed to address this drawback. Many of these methods, however, have
time complexity superlinear in the number of data points, which makes them
impractical for large data sets. On the other hand, linear methods are often
random and/or sensitive to the ordering of the data points. These methods are
generally unreliable in that the quality of their results is unpredictable.
Therefore, it is common practice to perform multiple runs of such methods and
take the output of the run that produces the best results. Such a practice,
however, greatly increases the computational requirements of the otherwise
highly efficient k-means algorithm. In this chapter, we investigate the
empirical performance of six linear, deterministic (non-random), and
order-invariant k-means initialization methods on a large and diverse
collection of data sets from the UCI Machine Learning Repository. The results
demonstrate that two relatively unknown hierarchical initialization methods due
to Su and Dy outperform the remaining four methods with respect to two
objective effectiveness criteria. In addition, a recent method due to Erisoglu
et al. performs surprisingly poorly.Comment: 21 pages, 2 figures, 5 tables, Partitional Clustering Algorithms
(Springer, 2014). arXiv admin note: substantial text overlap with
arXiv:1304.7465, arXiv:1209.196
Inflammatory responses to acute exercise during pulmonary rehabilitation in patients with COPD
Objective
Pulmonary rehabilitation is a cornerstone treatment in the management of chronic obstructive pulmonary disease (COPD). Acute bouts of exercise can lead to short bursts of inflammation in healthy individuals. However, it is unclear how COPD patients respond to acute bouts of exercise. This study assessed inflammatory responses to exercise in COPD patients at the start (phase 1) and end (phase 2) of pulmonary rehabilitation.
Methods
Blood samples were collected before and after an acute exercise bout at the start (phase 1, n = 40) and end (phase 2, n = 27) of pulmonary rehabilitation. The primary outcome was change in fibrinogen concentrations. Secondary outcomes were changes in CRP concentrations, total/differential leukocyte counts, markers of neutrophil activation (CD11b, CD62L and CD66b), and neutrophil subsets (mature, suppressive, immature, progenitor).
Results
Acute exercise (phase 1) did not induce significant changes in fibrinogen (p = 0.242) or CRP (p = 0.476). Total leukocyte count [mean difference (MD), 0.5 ± 1.1 (109 L−1); p = 0.004], neutrophil count [MD, 0.4 ± 0.8 (109 L−1); p < 0.001], and immature neutrophils (MD, 0.6 ± 0.8%; p < 0.001) increased post-exercise. Neutrophil activation markers, CD11b (p = 0.470), CD66b (p = 0.334), and CD62L (p = 0.352) were not significantly altered post-exercise. In comparison to the start of pulmonary rehabilitation (phase 2), acute exercise at the end of pulmonary rehabilitation led to a greater fibrinogen response (MD, 84 mg/dL (95% CI − 14, 182); p = 0.045).
Conclusion
An acute bout of exercise does not appear to induce significant alterations in the concentrations of inflammatory mediators but can increase white blood cell subsets post-exercise. A greater fibrinogen response to acute exercise is seen at the end of pulmonary rehabilitation when compared to the start. Further research is required to understand the clinical context of these acute inflammatory responses to exercise
Association of Panton Valentine Leukocidin (PVL) genes with methicillin resistant Staphylococcus aureus (MRSA) in Western Nepal: a matter of concern for community infections (a hospital based prospective study)
BACKGROUND: Methicillin resistant Staphylococcus aureus (MRSA) is a major human pathogen associated with nosocomial and community infections. Panton Valentine leukocidin (PVL) is considered one of the important virulence factors of S. aureus responsible for destruction of white blood cells, necrosis and apoptosis and as a marker of community acquired MRSA. This study was aimed to determine the prevalence of PVL genes among MRSA isolates and to check the reliability of PVL as marker of community acquired MRSA isolates from Western Nepal. METHODS: A total of 400 strains of S. aureus were collected from clinical specimens and various units (Operation Theater, Intensive Care Units) of the hospital and 139 of these had been confirmed as MRSA by previous study. Multiplex PCR was used to detect mecA and PVL genes. Clinical data as well as antimicrobial susceptibility data was analyzed and compared among PVL positive and negative MRSA isolates. RESULTS: Out of 139 MRSA isolates, 79 (56.8Â %) were PVL positive. The majority of the community acquired MRSA (90.4Â %) were PVL positive (Positive predictive value: 94.9Â % and negative predictive value: 86.6Â %), while PVL was detected only in 4 (7.1Â %) hospital associated MRSA strains. None of the MRSA isolates from hospital environment was found positive for the PVL genes. The majority of the PVL positive strains (75.5Â %) were isolated from pus samples. Antibiotic resistance among PVL negative MRSA isolates was found higher as compared to PVL positive MRSA. CONCLUSION: Our study showed high prevalence of PVL among community acquired MRSA isolates. Absence of PVL among MRSA isolates from hospital environment indicates its poor association with hospital acquired MRSA and therefore, PVL may be used a marker for community acquired MRSA. This is first study from Nepal, to test PVL among MRSA isolates from hospital environment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1531-1) contains supplementary material, which is available to authorized users
Feasibility of Tomotherapy-Based Image-Guided Radiotherapy to Reduce Aspiration Risk in Patients with Non-Laryngeal and Non-Pharyngeal Head and Neck Cancer
PURPOSE: The study aims to assess the feasibility of Tomotherapy-based image-guided radiotherapy (IGRT) to reduce the aspiration risk in patients with non-laryngeal and non-hypopharyngeal cancer. A retrospective review of 48 patients undergoing radiation for non-laryngeal and non-hypopharyngeal head and neck cancers was conducted. All patients had a modified barium swallow (MBS) prior to treatment, which was repeated one month following radiotherapy. Mean middle and inferior pharyngeal dose was recorded and correlated with the MBS results to determine aspiration risk. RESULTS: Mean pharyngeal dose was 23.2 Gy for the whole group. Two patients (4.2%) developed trace aspiration following radiotherapy which resolved with swallowing therapy. At a median follow-up of 19 months (1-48 months), all patients were able to resume normal oral feeding without aspiration. CONCLUSION AND CLINICAL RELEVANCE: IGRT may reduce the aspiration risk by decreasing the mean pharyngeal dose in the presence of large cervical lymph nodes. Further prospective studies with IGRT should be performed in patients with non-laryngeal and non-hypopharyngeal head and neck cancers to verify this hypothesis
Modeling Evolutionary Dynamics of Epigenetic Mutations in Hierarchically Organized Tumors
The cancer stem cell (CSC) concept is a highly debated topic in cancer research.
While experimental evidence in favor of the cancer stem cell theory is
apparently abundant, the results are often criticized as being difficult to
interpret. An important reason for this is that most experimental data that
support this model rely on transplantation studies. In this study we use a novel
cellular Potts model to elucidate the dynamics of established malignancies that
are driven by a small subset of CSCs. Our results demonstrate that epigenetic
mutations that occur during mitosis display highly altered dynamics in
CSC-driven malignancies compared to a classical, non-hierarchical model of
growth. In particular, the heterogeneity observed in CSC-driven tumors is
considerably higher. We speculate that this feature could be used in combination
with epigenetic (methylation) sequencing studies of human malignancies to prove
or refute the CSC hypothesis in established tumors without the need for
transplantation. Moreover our tumor growth simulations indicate that CSC-driven
tumors display evolutionary features that can be considered beneficial during
tumor progression. Besides an increased heterogeneity they also exhibit
properties that allow the escape of clones from local fitness peaks. This leads
to more aggressive phenotypes in the long run and makes the neoplasm more
adaptable to stringent selective forces such as cancer treatment. Indeed when
therapy is applied the clone landscape of the regrown tumor is more aggressive
with respect to the primary tumor, whereas the classical model demonstrated
similar patterns before and after therapy. Understanding these often
counter-intuitive fundamental properties of (non-)hierarchically organized
malignancies is a crucial step in validating the CSC concept as well as
providing insight into the therapeutical consequences of this model
SDS-PAGE-Based Quantitative Assay for Screening of Kidney Stone Disease
Kidney stone disease is a common health problem in industrialised nations. We developed a SDS-PAGE-based method to quantify Tamm Horsfall glycoprotein (THP) for screening of kidney stone disease. Urinary proteins were extracted by using ammonium sulphate precipitation at 0.27 g salt/mL urine. The resulted pellet was dissolved in TSE buffer. Ten microliters of the urinary proteins extract was loaded and separated on 10% SDS-PAGE under reducing condition. THP migrated as single band in SDS-PAGE. The assay reproducibility and repeatability were 4.8% CV and 2.6% CV, respectively. A total of 117 healthy subjects and 58 stone patients were tested using this assay, and a distinct cut-off (P < 0.05) at 5.6 μg/mL THP concentration was used to distinguish stone patients from healthy subjects. The sensitivity and specificity of the method were 92.3% and 83.3%, respectively
Treatment-Induced Tumor Dormancy through YAP-Mediated Transcriptional Reprogramming of the Apoptotic Pathway
Eradicating tumor dormancy that develops following epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment of EGFR-mutant non-small cell lung cancer, is an attractive therapeutic strategy but the mechanisms governing this process are poorly understood. Blockade of ERK1/2 reactivation following EGFR TKI treatment by combined EGFR/MEK inhibition uncovers cells that survive by entering a senescence-like dormant state characterized by high YAP/TEAD activity. YAP/TEAD engage the epithelial-to-mesenchymal transition transcription factor SLUG to directly repress pro-apoptotic BMF, limiting drug-induced apoptosis. Pharmacological co-inhibition of YAP and TEAD, or genetic deletion of YAP1, all deplete dormant cells by enhancing EGFR/MEK inhibition-induced apoptosis. Enhancing the initial efficacy of targeted therapies could ultimately lead to prolonged treatment responses in cancer patients
Culture Adaptation Alters Transcriptional Hierarchies among Single Human Embryonic Stem Cells Reflecting Altered Patterns of Differentiation
We have used single cell transcriptome analysis to re-examine the substates of early passage, karyotypically Normal, and late passage, karyotypically Abnormal (‘Culture Adapted’) human embryonic stem cells characterized by differential expression of the cell surface marker antigen, SSEA3. The results confirmed that culture adaptation is associated with alterations to the dynamics of the SSEA3(+) and SSEA3(-) substates of these cells, with SSEA3(-) Adapted cells remaining within the stem cell compartment whereas the SSEA3(-) Normal cells appear to have differentiated. However, the single cell data reveal that these substates are characterized by further heterogeneity that changes on culture adaptation. Notably the Adapted population includes cells with a transcriptome substate suggestive of a shift to a more naïve-like phenotype in contrast to the cells of the Normal population. Further, a subset of the Normal SSEA3(+) cells expresses genes typical of endoderm differentiation, despite also expressing the undifferentiated stem cell genes, POU5F1 (OCT4) and NANOG, whereas such apparently lineage-primed cells are absent from the Adapted population. These results suggest that the selective growth advantage gained by genetically variant, culture adapted human embryonic stem cells may derive in part from a changed substate structure that influences their propensity for differentiation
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