269 research outputs found

    Patient experiences at a high-risk pancreatic cancer clinic: A thematic analysis of focus groups

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    Pancreatic cancer is a rare, occurring in less than 2% of the population, but high mortality disease with a survival rate of less than 6%. Approximately 5-10% of pancreatic cancer is due to a hereditary predisposition. A hereditary predisposition may be due to a pathogenic variant within a gene related to cancer syndromes, or some individuals may also be at risk due to having two or more first-degree relatives or three or more close family members who have been diagnosed with pancreatic cancer, which is considered Familial Pancreatic Cancer. This study focuses on these individuals who are at an increased risk of developing pancreatic cancer and their caregivers. The goal of this study is to identify patients’ experiences at a high-risk pancreatic cancer center in Pittsburgh, Pennsylvania, and their experiences of living with a family history of pancreatic cancer. Participants of the larger Pancreatic Adenocarcinoma Gene Environment Risk (PAGER) Study and their caregivers were invited to attend one of two focus groups where they were able to provide their opinions and comments about the clinic and their feelings of living with an increased risk of pancreatic cancer. Transcripts of the focus groups were analyzed by qualitative thematic analysis, which identified five major themes. The main themes identified were: 1. Attributes study participants noted about the clinic staff; 2. Barriers individuals faced to receiving care; 3. The fear participants described related to being at an increased risk to develop pancreatic cancer; 4. The family dynamics surrounding the increased risk for pancreatic cancer; and 5. Areas of improvement identified by participants for the clinic and pancreatic cancer research in general. The results of this study identified overwhelming satisfaction with the UPMC High-Risk Pancreas Clinic and the care that is provided to the patients in the clinic. Public Health Significance: This study has public health significance because it has been shown that patients who are satisfied with their care experience better health outcomes

    masstodon: A Tool for Assigning Peaks and Modeling Electron Transfer Reactions in Top-Down Mass Spectrometry

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    Top-down mass spectrometry methods are becoming continuously more popular in the effort to describe the proteome. They rely on the fragmentation of intact protein ions inside the mass spectrometer. Among the existing fragmentation methods, electron transfer dissociation is known for its precision and wide coverage of different cleavage sites. However, several side reactions can occur under electron transfer dissociation (ETD) conditions, including nondissociative electron transfer and proton transfer reaction. Evaluating their extent can provide more insight into reaction kinetics as well as instrument operation. Furthermore, preferential formation of certain reaction products can reveal important structural information. To the best of our knowledge, there are currently no tools capable of tracing and analyzing the products of these reactions in a systematic way. In this Article, we present in detail masstodon: a computer program for assigning peaks and interpreting mass spectra. Besides being a general purpose tool, masstodon also offers the possibility to trace the products of reactions occurring under ETD conditions and provides insights into the parameters driving them. It is available free of charge under the GNU AGPL V3 public license

    A Coverage Criterion for Spaced Seeds and its Applications to Support Vector Machine String Kernels and k-Mer Distances

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    Spaced seeds have been recently shown to not only detect more alignments, but also to give a more accurate measure of phylogenetic distances (Boden et al., 2013, Horwege et al., 2014, Leimeister et al., 2014), and to provide a lower misclassification rate when used with Support Vector Machines (SVMs) (On-odera and Shibuya, 2013), We confirm by independent experiments these two results, and propose in this article to use a coverage criterion (Benson and Mak, 2008, Martin, 2013, Martin and No{\'e}, 2014), to measure the seed efficiency in both cases in order to design better seed patterns. We show first how this coverage criterion can be directly measured by a full automaton-based approach. We then illustrate how this criterion performs when compared with two other criteria frequently used, namely the single-hit and multiple-hit criteria, through correlation coefficients with the correct classification/the true distance. At the end, for alignment-free distances, we propose an extension by adopting the coverage criterion, show how it performs, and indicate how it can be efficiently computed.Comment: http://online.liebertpub.com/doi/abs/10.1089/cmb.2014.017

    Batoid abundances, spatial distribution, and life history traits in the strait of sicily (Central mediterranean sea): Bridging a knowledge gap through three decades of survey

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    Batoid species play a key role in marine ecosystems but unfortunately they have globally declined over the last decades. Given the paucity of information, abundance data and the main life history traits for batoids, obtained through about three decades of bottom trawl surveys, are presented and discussed. The surveys were carried out in two areas of the Central Mediterranean (South of Sicily and Malta Island), in a timeframe ranging from 1990 to 2018. Excluding some batoids, the abundance trends were stable or increasing. Only R. clavata, R. miraletus, and D. oxyrinchus showed occurrence and abundance indexes notable enough to carry out more detailed analysis. In particular, spatial distribution analysis of these species highlighted the presence of two main hotspots in Sicilian waters whereas they seem more widespread in Malta. The lengths at first maturity (L50) were 695 and 860, 635 and 574, and 364 and 349 mm total length (TL), respectively, for females and males of D. oxyrinchus, R. clavata, and R. miraletus. The asymptotic lengths (L∞) and the curvature coefficients (K) were 1365 and 1240 (K = 0.11 and 0.26), 1260 and 1100 (K = 0.16 and 0.26), and 840 and 800 mm TL (K = 0.36 and 0.41), respectively, for females and males of D. oxyrinchus, R. clavata, and R. miraletus. The lack of detailed quantitative historical information on batoids of Sicily and Malta does not allow to analytically judge the current status of the stocks, although the higher abundance of some species within Malta raises some concern for the Sicilian counterpart. In conclusion, suitable actions to protect batoids in the investigated area are recommended

    Reply to comment by C. Morhange, C. Flaux, P.A. Pirazzoli, M.B. Carre on \u201cHolocene Sea level Change in Malta\u201d

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    The pits of Birzebbugia are located near the present-day mean sea level, and some are partially submerged. They were dated using pottery discovered in an archaeological site close to the coast, dated to the Bronze Age (Zammit, 1928; Abela, 1999). As they have been interpreted as sites for the retting of flax, during their utilization they should have remained dry and the sea could not submerge them. This is the reason why these structures are not directly related to the sea level, as suggested by Biolchi et al. (2011), so they represent an upper limit.peer-reviewe

    Estimation of Rates of Reactions Triggered by Electron Transfer in Top-Down Mass Spectrometry

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    Electron transfer dissociation (ETD) is a versatile technique used in mass spectrometry for the high-throughput characterization of proteins. It consists of several concurrent reactions triggered by the transfer of an electron from its anion source to sample cations. Transferring an electron causes peptide backbone cleavage while leaving labile post-translational modifications intact. The obtained fragmentation spectra provide valuable information for sequence and structure analyses. In this study, we propose a formal mathematical model of the ETD fragmentation process in the form of a system of stochastic differential equations describing its joint dynamics. Parameters of the model correspond to the rates of occurring reactions. Their estimates for various experimental settings give insight into the dynamics of the ETD process. We estimate the model parameters from the relative quantities of fragmentation products in a given mass spectrum by solving a nonlinear optimization problem. The cost function penalizes for the differences between the analytically derived average number of reaction products and their experimental counterparts. The presented method proves highly robust to noise in silico. Moreover, the model can explain a considerable amount of experimental results for a wide range of instrumentation settings. The implementation of the presented workflow, code-named ETDetective, is freely available under the two-clause BSD license

    Inferring serum proteolytic activity from LC-MS/MS data

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    <p>Abstract</p> <p>Background</p> <p>In this paper we deal with modeling serum proteolysis process from tandem mass spectrometry data. The parameters of peptide degradation process inferred from LC-MS/MS data correspond directly to the activity of specific enzymes present in the serum samples of patients and healthy donors. Our approach integrate the existing knowledge about peptidases' activity stored in MEROPS database with the efficient procedure for estimation the model parameters.</p> <p>Results</p> <p>Taking into account the inherent stochasticity of the process, the proteolytic activity is modeled with the use of Chemical Master Equation (CME). Assuming the stationarity of the Markov process we calculate the expected values of digested peptides in the model. The parameters are fitted to minimize the discrepancy between those expected values and the peptide activities observed in the MS data. Constrained optimization problem is solved by Levenberg-Marquadt algorithm.</p> <p>Conclusions</p> <p>Our results demonstrates the feasibility and potential of high-level analysis for LC-MS proteomic data. The estimated enzyme activities give insights into the molecular pathology of colorectal cancer. Moreover the developed framework is general and can be applied to study proteolytic activity in different systems.</p

    Correspondence Between Cognitive and Audiological Evaluations Among the Elderly: A Preliminary Report of an Audiological Screening Model of Subjects at Risk of Cognitive Decline With Slight to Moderate Hearing Loss

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    Epidemiological studies show increasing prevalence rates of cognitive decline and hearing loss with age, particularly after the age of 65 years. These conditions are reported to be associated, although conclusive evidence of causality and implications is lacking. Nevertheless, audiological and cognitive assessment among elderly people is a key target for comprehensive and multidisciplinary evaluation of the subject's frailty status. To evaluate the use of tools for identifying older adults at risk of hearing loss and cognitive decline and to compare skills and abilities in terms of hearing and cognitive performances between older adults and young subjects, we performed a prospective cross-sectional study using supraliminal auditory tests. The relationship between cognitive assessment results and audiometric results was investigated, and reference ranges for different ages or stages of disease were determined. Patients older than 65 years with different degrees of hearing function were enrolled. Each subject underwent an extensive audiological assessment, including tonal and speech audiometry, Italian Matrix Sentence Test, and speech audiometry with logatomes in quiet. Cognitive function was screened and then verified by experienced clinicians using the Montreal Cognitive Assessment Score, the Geriatric Depression Scale, and further investigations in some. One hundred twenty-three subjects were finally enrolled during 2016-2019: 103 were >65 years of age and 20 were younger participants (as controls). Cognitive functions showed a correlation with the audiological results in post-lingual hearing-impaired patients, in particular in those affected by slight to moderate hearing loss and aged more than 70 years. Audiological testing can thus be useful in clinical assessment and identification of patients at risk of cognitive impairment. The study was limited by its sample size (CI 95%; CL 10%), strict dependence on language, and hearing threshold. Further investigations should be conducted to confirm the reported results and to verify similar screening models
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