154 research outputs found
Stochastic Gene Expression in Cells: A Point Process Approach
This paper investigates the stochastic fluctuations of the number of copies
of a given protein in a cell. This problem has already been addressed in the
past and closed-form expressions of the mean and variance have been obtained
for a simplified stochastic model of the gene expression. These results have
been obtained under the assumption that the duration of all the protein
production steps are exponentially distributed. In such a case, a Markovian
approach (via Fokker-Planck equations) is used to derive analytic formulas of
the mean and the variance of the number of proteins at equilibrium. This
assumption is however not totally satisfactory from a modeling point of view
since the distribution of the duration of some steps is more likely to be
Gaussian, if not almost deterministic. In such a setting, Markovian methods can
no longer be used. A finer characterization of the fluctuations of the number
of proteins is therefore of primary interest to understand the general economy
of the cell. In this paper, we propose a new approach, based on marked Poisson
point processes, which allows to remove the exponential assumption. This is
applied in the framework of the classical three stages models of the
literature: transcription, translation and degradation. The interest of the
method is shown by recovering the classical results under the assumptions that
all the durations are exponentially distributed but also by deriving new
analytic formulas when some of the distributions are not anymore exponential.
Our results show in particular that the exponential assumption may,
surprisingly, underestimate significantly the variance of the number of
proteins when some steps are in fact not exponentially distributed. This
counter-intuitive result stresses the importance of the statistical assumptions
in the protein production process
Esophageal atresia and tracheo-esophageal fistula in Western Australia: prevelence and trends
Objectives A recent international study reported a higher prevalence of esophageal atresia with or without tracheo-esophageal fistula (EA±TEF) in Western Australia (WA). The aim of this study was to examine the prevalence and trends of EA and/or TEF in WA; determine the proportion of cases with associated anomalies; and explore the impact of time of diagnosis. Methods The study population comprised all infants born in WA, 1980-2009 and registered with EA and/or TEF on the WA Register of Developmental Anomalies (WARDA). Results EA±TEF and TEF alone affect, on average, 1 in every 2,927 births in WA, with a total prevalence of 3.00 and 0.42 per 10,000 births, respectively. The prevalence of EA±TEF increased by 2.0% per annum, with only cases with associated anomalies (64% of cases) demonstrating an increase. TEF rates were stable. Among EA±TEF infants, the proportion of live births, stillbirths and elective terminations of pregnancy for fetal anomaly (TOPFA) was 79%, 6% and 15%, respectively; while the majority (94%) of TEF only cases were live births. In 2000-2009 there was 30% fall in EA±TEF live births with 61 (58%) cases diagnosed in first week of life, 10 (9%) prenatally and 34 (32%) at postmortem only. Conclusions A higher prevalence of EA±TEF in WA was observed with increase over time attributable to increase with associated anomalies. Consistent reporting, availability of prenatal diagnosis and ascertainment of cases following TOPFA or postmortem examinations can significantly affect prevalence of EA and/or TEF.NHMR
Evaluation of the endorsement of the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement on the quality of published systematic review and meta-analyses.
Introduction PRISMA statement was published in 2009 in order to set standards in the reporting of systematic reviews and meta-analyses. Our aim was to evaluate the impact of PRISMA endorsement on the quality of reporting and methodological quality of systematic reviews and meta-analyses, published in journals in the field of gastroenterology and hepatology (GH). Methods Quality of reporting and methodological quality were evaluated by assessing the adherence of papers to PRISMA checklist and AMSTAR quality scale. After identifying the GH journals which endorsed PRISMA in instructions for authors (IA), we appraised: 15 papers published in 2012 explicitly mentioning PRISMA in the full text (Group A); 15 papers from the same journals published in 2012 not explicitly mentioning PRISMA in the full text (Group B); 30 papers published the year preceding PRISMA endorsement from the same journals as above (Group C); 30 papers published in 2012 on the 10 highest impact factor journals in GH which not endorsed PRISMA (Group D). Results PRISMA statement was referred in the IA in 9 out of 70 GH journals (12.9%). We found significant increase in overall adherence to PRISMA checklist (Group A, 90.1%; Group C, 83.1%; p = 0.003) and compliance to AMSTAR scale (Group A, 85.0%; Group C, 74.6%; p = 0.002), following the PRISMA endorsement from the nine GH journals. Explicit referencing of PRISMA in manuscript was not associated with increase in quality of reporting and methodological quality (Group A vs. B, p = 0.651, p = 0.900, respectively). Adherence to PRISMA checklist, and the compliance with AMSTAR were significantly higher in journals endorsing PRISMA compared to those not (Groups A+B vs. D; p = 0.003 and p = 0.016, respectively). Conclusion The endorsement of PRISMA resulted in increase of both quality of reporting and methodological quality. It is advised that an increasing number of medical journals include PRISMA in the instructions for authors
Sociodemographic determinants of knowledge on the figure of radiologist: results of a survey in large university hospital
Introduction
Despite overlaying an irreplaceable role as a key diagnostic tool in modern medicine, the role of radiologist still appears to be unclear to patients.
Methods We conducted a survey in outpatient clinic of Radiological Sciences Department of the University Hospital “A. Gemelli” in Rome, aiming to assess how correct patients identify the figure of the radiologist. The patients were interviewed by the trained physician using structured questionnaire.
Results We included the number of 259 patients. Majority were female 63.3%, most were 60-69 years old (24.3%), have finished second grade secondary school (35.1%) and were subjected to magnetic resonance (28.6%) while the least were subjected to chest X-ray (8.1%). Only 38.7% answered correctly to question No 1 “Who performed your examination?”, and only 30.9% correctly identified the radiologist as a person interpreting the exam (question No 2 “Who is going to interpret your radiological examination?”). Overall, 16.8% responded correctly to the both questions. Significantly less patients with primary school (OR: 0.18, CI 95% 0.06-0.49) and first grade secondary school (OR: 0.37, CI 95% 0.18-0.75) correctly addressed the question No 1 in compare to those with second grade secondary school. The first grade secondary education (OR: 0.43, CI 95% 0.20-0.92) was inversely associated with correct answer to question No 2. Patients with primary education were significantly less prone to give both correct answers (OR: 0.12, CI 95% 0.02-0.60).
Conclusion We report insufficient knowledge among patients on radiologist’s role in healthcare system. The level of knowledge is associated with level of education
Progress towards making a global supply of microbial extracellular vesicles,100-times cheaper than a typical biologic
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IGHV mutational status of nodal marginal zone lymphoma by NGS reveals distinct pathogenic pathways with different prognostic implications
The precise B cell of origin and molecular pathogenesis of nodal marginal zone lymphoma (NMZL) remain poorly defined. To date, due to the rarity of NMZL, the vast majority of already-published studies have been conducted on a limited number of samples and the technical approach to analyze the immunoglobulin genes was of amplifying rearranged variable region genes with the classical direct sequencing of the PCR products followed by cloning. Here, we studied the B cell Ig heavy-chain repertoires by next-generation sequencing (NGS) in 30 NMZL cases. Most of the cases were mutated (20/28; 71.5%) with homologies to the respective germ line genes ranging from 85 to 97, 83%, whereas 8/28 (28.5%) were unmutated. In addition, our results show that NMZL cases have a biased usage of specific immunoglobulin heavy-chain variable (IGHV) region genes. Moreover, we documented intraclonal diversity in all (100%) of the mutated cases and ongoing somatic hypermutations (SHM) have been confirmed by hundreds of reads. We analyzed the mutational pattern to detect and quantify antigen selection pressure and we found a positive selection in 4 cases, whereas in the remaining cases there was an unspecific stimulation. Finally, the disease-specific survival and the progression-free survival were significantly different between cases with mutated and unmutated IGHV genes, pointing out mutational status as a possible new biomarker in NMZL
Peripheral artery disease and blood pressure profile abnormalities in hemodialysis patients
Patients undergoing chronic hemodialysis (HD) are at increased risk for peripheral artery disease (PAD). Both ankle-brachial index (ABI) and ambulatory blood pressure monitoring (ABPM) in the interdialytic period have been shown to be strong predictors of all-cause mortality
Cyclopia: An epidemiologic study in a large dataset from the International Clearinghouse of Birth Defects Surveillance and Research
Cyclopia is characterized by the presence of a single eye, with varying degrees of doubling of the intrinsic ocular structures, located in the middle of the face. It is the severest facial expression of the holoprosencephaly (HPE) spectrum. This study describes the prevalence, associated malformations, and maternal characteristics among cases with cyclopia. Data originated in 20 Clearinghouse (ICBDSR) affiliated birth defect surveillance systems, reported according to a single pre-established protocol. A total of 257 infants with cyclopia were identified. Overall prevalence was 1 in 100,000 births (95%CI: 0.89-1.14), with only one program being out of range. Across sites, there was no correlation between cyclopia prevalence and number of births (r=0.08; P=0.75) or proportion of elective termination of pregnancy (r=-0.01; P=0.97). The higher prevalence of cyclopia among older mothers (older than 34) was not statistically significant. The majority of cases were liveborn (122/200; 61%) and females predominated (male/total: 42%). A substantial proportion of cyclopias (31%) were caused by chromosomal anomalies, mainly trisomy 13. Another 31% of the cases of cyclopias were associated with defects not typically related to HPE, with more hydrocephalus, heterotaxia defects, neural tube defects, and preaxial reduction defects than the chromosomal group, suggesting the presence of ciliopathies or other unrecognized syndromes. Cyclopia is a very rare defect without much variability in prevalence by geographic location. The heterogeneous etiology with a high prevalence of chromosomal abnormalities, and female predominance in HPE, were confirmed, but no effect of increased maternal age or association with twinning was observed.Fil: Orioli, Ieda Maria. Instituto de Biologia; Brasil. Instituto Nacional de GenĂ©tica MĂ©dica Populacional; BrasilFil: Amar, Emmanuelle. Rhone-alps Registry Of Birth Defects Remera; FranciaFil: Bakker, Marian K.. University of Groningen; PaĂses BajosFil: Bermejo Sánchez, Eva. Instituto de Salud Carlos III; Brasil. Centro de InvestigaciĂłn BiomĂ©dica En Red de Enfermedades Raras; BrasilFil: Bianchi, Fabrizio. Consiglio Nazionale delle Ricerche; ItaliaFil: Canfield, Mark A.. Texas Department Of State Health Services; Estados UnidosFil: Clementi, Maurizio. UniversitĂ di Padova; ItaliaFil: Correa, Adolfo. Centers for Disease Control and Prevention; BrasilFil: Csáky Szunyogh, Melinda. National Center for Healthcare Audit and Inspection; HungrĂaFil: Feldkamp, Marcia L.. Utah Department Of Health; Estados Unidos. University Of Utah Health Sciences; Estados UnidosFil: Landau, Danielle. Soroka University Medical Center; IsraelFil: Leoncini, Emanuele. Centre Of The International Clearinghouse For Birth Defects Surveillance And Research; ItaliaFil: Li, Zhu. Peking University Health Science Center; ChinaFil: Lowry, R. Brian. Alberta Congenital Anomalies Surveillance System; CanadáFil: Mastroiacovo, Pierpaolo. Centre Of The International Clearinghouse For Birth Defects Surveillance And Research; ItaliaFil: Morgan, Margery. the Congenital Anomaly Register for Wales; Reino UnidoFil: Mutchinick, Osvaldo M.. Instituto Nacional de la NutriciĂłn Salvador Zubiran; MĂ©xicoFil: Rissmann, Anke. Otto-von-Guericke-Universität Magdeburg; AlemaniaFil: Ritvanen, Annukka. National Institute For Health And Welfare; FinlandiaFil: Scarano, Gioacchino. General Hospital G. Rummo Benevento; ItaliaFil: Szabova, Elena. Slovak Medical University; EslovaquiaFil: Castilla, Eduardo Enrique. Instituto Nacional de GenĂ©tica MĂ©dica Populacional; Brasil. Centro de EducaciĂłn Medica E Invest.clinicas; Argentina. FundaciĂłn Oswaldo Cruz; Brasil. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentin
Increased incidence trend of low-grade and high-grade neuroendocrine neoplasms
Purpose: The incidence of neuroendocrine neoplasms is increasing. This work aimed at: (i) establishing worldwide incidence trend of low-grade neuroendocrine neoplasms; (ii) defining the incidence and temporal trend of high-grade neuroendocrine neoplasms in USA utilizing the Surveillance Epidemiology and End Results database; (iii) comparing trends for low-grade vs. high-grade neuroendocrine neoplasms. Methods: We conducted a literature search on MEDLINE and Scopus databases and incidence trends were plotted for 1973-2012. The Surveillance Epidemiology and End Results database was used to identify incidence rates in USA for 1973-2012. Incidence rates were stratified according to histological grade, gender and ethnicity. Trends were summarized as annual percent change and corresponding 95% confidence interval. Results: 11 studies were identified involving 72,048 cases; neuroendocrine neoplasm incidence rates increased over time in all countries for all sites, except for appendix. In Surveillance Epidemiology and End Results low-grade neuroendocrine neoplasm incidence rate increased from 1.09 in 1973 to 3.51 per 100,000 in 2012. During this interval, high-grade neuroendocrine neoplasm incidence rate increased from 2.54 to 10.52 per 100,000. African Americans had the highest rates of digestive neuroendocrine neoplasms with male prevalence in high-grade. Conclusions: Our data indicate an increase in the incidence of neuroendocrine neoplasms as a worldwide phenomenon, affecting most anatomical sites and involving both low-grade and high-grade neoplasms. © 2017, The Author(s)
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