426 research outputs found

    Lipid droplet detection by the cavity perturbation method

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    There are currently no point-of-care diagnosis strategies available to indicate the presence of neoplasmic growth. This research aims to develop a novel diagnostic strategy based on detecting TAG accumulation in cells. This element of the research is a preliminary experiment to prove the concept of detecting TAG lipid droplets in YEPD media. It was found that a change in mono-unsaturated concentration can be detected by the frequency shift in a resonant cavity. The dielectric constant of TAG vegetable oils was calculated at 2.34-2.39. It was also found that concentrations of lipid droplet can be differentiated up to 5% (v/v)

    Summer Distribution of Bowhead Whales, Balaena mysticetus, Relative to Oil Industry Activities in the Canadian Beaufort Sea, 1980-84

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    Aerial surveys in 1980-84 showed that summer distribution of bowheads in the Beaufort Sea varied markedly between years. Distribution varied both outside and within the "main industrial area" (MIA), the area of island construction, drilling and intensive ship and helicopter traffic. Numbers of bowheads in the MIA were high in 1980, lower in 1981, near zero in 1982 and very low in 1983-84. The few whales in the MIA in 1983-84 were mainly near its edges, contrary to 1980-81. These data, plus limited evidence from 1976-79, indicate that bowheads were numerous in the centre of the MIA in 3 of 5 years from 1976-80 (1976-77, 1980) vs. 0 of 4 years from 1981-84. One hypothesis is that progressively increasing industrial activities affected bowhead distribution after 1980. However, bowheads probably also react to variations in their zooplankton prey, which may be affected by year-to-year changes in oceanography and weather. Influences of natural factors on zooplankton and bowheads need to be better understood in order to assess whether oil exploration caused any of the observed changes in bowhead distribution.Key words: bowhead whale, Balaena mysticetus, Beaufort Sea, oil exploration, seismic exploration, aerial surveysDes relevés aériens effectués entre 1980 et 1984 ont montré que la répartition estivale des baleines franches dans la mer de Beaufort varie nettement d’année en année. Elle varie à fois à l’extérieure et à l’intérieur de la “zone industrielle principale” (ZIP), qui est la zone de construction de l’île, de forage et de circulation intense de bateaux et d’hélicoptères. Le nombre de baleines franches dans la ZIP était élevé en 1980, plus bas en 1981, près de zéro en 1982, et très bas en 1983 et 1984. Les quelques baleines présentes dans la ZIP en 1983 et 1984 étaient principalement à la périphérie, contrairement à 1980 et 1981. Ces données, jointes à des évidences plus limitées de 1976 à 1979, indiquent que les baleines franches étaient nombreuses au centre de la ZIP pendant 3 années sur 5, allant de 1976 à 1980 (1976, 1977 et 1980), par rapport à aucune année sur les quatre allant de 1981 à 1984. On avance l’hypothèse que les activités industrielles progressivement croissantes ont affecté la répartition des baleines franches après 1980. Cependant, les baleines franches ont probablement réagi aussi aux variations de zooplancton qui constitue leur nourriture et qui peut être affecté par les changements qui ont lieu d’année en année dans l’océanographie et le climat. I1 est nécessaire de mieux comprendre l’influence des facteurs naturels sur le zooplancton et les baleines franches afin d’évaluer si l’exploration pétrolière a provoqué l’un quelconque des changements observés dans la répartition de ces baleines.Mots clés: baleine franche, Balaena mysticetus, mer de Beaufort, exploration pétrolière, exploration sismique, relevés aérien

    Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

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    Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

    Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging

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    Objective: The purpose of this study was to explore the diagnostic yield and clinical utility of trio-based rapid whole exome sequencing (rWES) in pregnancies of fetuses with a wide range of congenital anomalies detected by ultrasound imaging. Methods: In this observational study, we analyzed the first 54 cases referred to our laboratory for prenatal rWES to support clinical decision making, after the sonographic detection of fetal congenital anomalies. The most common identified congenital anomalies were skeletal dysplasia (n = 20), multiple major fetal congenital anomalies (n = 17) and intracerebral structural anomalies (n = 7). Results: A conclusive diagnosis was identified in 18 of the 54 cases (33%). Pathogenic variants were detected most often in fetuses with skeletal dysplasia (n = 11) followed by fetuses with multiple major fetal congenital anomalies (n = 4) and intracerebral structural anomalies (n = 3). A survey, completed by the physicians for 37 of 54 cases, indicated that the rWES results impacted clinical decision making in 68% of cases. Conclusions: These results suggest that rWES improves prenatal diagnosis of fetuses with congenital anomalies, and has an important impact on prenatal and peripartum parental and clinical decision making

    A pan-Arctic initiative on the spatial and temporal dynamics of Arctic coasts

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    Permafrost coasts make up roughly one third of all coasts worldwide. Their erosion leads to the release of previously locked organic carbon, changes in ecosystems and the destruction of cultural heritage, infrastructure and whole communities. Since rapid environmental changes lead to an intensification of Arctic coastal dynamics, it is of great importance to adequately quantify current and future coastal changes. However, the remoteness of the Arctic and scarcity of data limit our understanding of coastal dynamics at a pan-Arctic scale and prohibit us from getting a complete picture of the diversity of impacts on the human and natural environment. In a joint effort of the EU project NUNATARYUK and the NSF project PerCS-Net, we seek to close this knowledge gap by collecting and analyzing all accessible high-resolution shoreline position data for the Arctic coastline. These datasets include geographical coordinates combined with coastal positions derived from archived data, surveying data, air and space born remote sensing products, or LiDAR products. The compilation of this unique dataset will enable us to reach unprecedented data coverage and will allow us a first insight into the magnitude and trends of shoreline changes on a pan-Arctic scale with locally highly resolved temporal and spatial changes in shoreline dynamics. By comparing consistently derived shoreline change data from all over the Arctic we expect that the trajectory of coastal change in the Arctic becomes evident. A synthesis of some initial results will be presented in the 2020 Arctic Report Card on Arctic Coastal Dynamics. This initiative is an ongoing effort – new data contributions are welcome

    Rapid exome sequencing as a first-tier test in neonates with suspected genetic disorder:results of a prospective multicenter clinical utility study in the Netherlands

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    The introduction of rapid exome sequencing (rES) for critically ill neonates admitted to the neonatal intensive care unit has made it possible to impact clinical decision-making. Unbiased prospective studies to quantify the impact of rES over routine genetic testing are, however, scarce. We performed a clinical utility study to compare rES to conventional genetic diagnostic workup for critically ill neonates with suspected genetic disorders. In a multicenter prospective parallel cohort study involving five Dutch NICUs, we performed rES in parallel to routine genetic testing for 60 neonates with a suspected genetic disorder and monitored diagnostic yield and the time to diagnosis. To assess the economic impact of rES, healthcare resource use was collected for all neonates. rES detected more conclusive genetic diagnoses than routine genetic testing (20% vs. 10%, respectively), in a significantly shorter time to diagnosis (15 days (95% CI 10–20) vs. 59 days (95% CI 23–98, p &lt; 0.001)). Moreover, rES reduced genetic diagnostic costs by 1.5% (€85 per neonate). Conclusion: Our findings demonstrate the clinical utility of rES for critically ill neonates based on increased diagnostic yield, shorter time to diagnosis, and net healthcare savings. Our observations warrant the widespread implementation of rES as first-tier genetic test in critically ill neonates with disorders of suspected genetic origin.What is Known:• Rapid exome sequencing (rES) enables diagnosing rare genetic disorders in a fast and reliable manner, but retrospective studies with neonates admitted to the neonatal intensive care unit (NICU) indicated that genetic disorders are likely underdiagnosed as rES is not routinely used.• Scenario modeling for implementation of rES for neonates with presumed genetic disorders indicated an expected increase in costs associated with genetic testing.What is New:• This unique prospective national clinical utility study of rES in a NICU setting shows that rES obtained more and faster diagnoses than conventional genetic tests.• Implementation of rES as replacement for all other genetic tests does not increase healthcare costs but in fact leads to a reduction in healthcare costs.</p

    Generalization of DNA microarray dispersion properties: microarray equivalent of t-distribution

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    BACKGROUND: DNA microarrays are a powerful technology that can provide a wealth of gene expression data for disease studies, drug development, and a wide scope of other investigations. Because of the large volume and inherent variability of DNA microarray data, many new statistical methods have been developed for evaluating the significance of the observed differences in gene expression. However, until now little attention has been given to the characterization of dispersion of DNA microarray data. RESULTS: Here we examine the expression data obtained from 682 Affymetrix GeneChips(® )with 22 different types and we demonstrate that the Gaussian (normal) frequency distribution is characteristic for the variability of gene expression values. However, typically 5 to 15% of the samples deviate from normality. Furthermore, it is shown that the frequency distributions of the difference of expression in subsets of ordered, consecutive pairs of genes (consecutive samples) in pair-wise comparisons of replicate experiments are also normal. We describe a consecutive sampling method, which is employed to calculate the characteristic function approximating standard deviation and show that the standard deviation derived from the consecutive samples is equivalent to the standard deviation obtained from individual genes. Finally, we determine the boundaries of probability intervals and demonstrate that the coefficients defining the intervals are independent of sample characteristics, variability of data, laboratory conditions and type of chips. These coefficients are very closely correlated with Student's t-distribution. CONCLUSION: In this study we ascertained that the non-systematic variations possess Gaussian distribution, determined the probability intervals and demonstrated that the K(α )coefficients defining these intervals are invariant; these coefficients offer a convenient universal measure of dispersion of data. The fact that the K(α )distributions are so close to t-distribution and independent of conditions and type of arrays suggests that the quantitative data provided by Affymetrix technology give "true" representation of physical processes, involved in measurement of RNA abundance. REVIEWERS: This article was reviewed by Yoav Gilad (nominated by Doron Lancet), Sach Mukherjee (nominated by Sandrine Dudoit) and Amir Niknejad and Shmuel Friedland (nominated by Neil Smalheiser)

    IL-6-Mediated Activation of Stat3α Prevents Trauma/Hemorrhagic Shock-Induced Liver Inflammation

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    Trauma complicated by hemorrhagic shock (T/HS) is the leading cause of morbidity and mortality in the United States for individuals under the age of 44 years. Initial survivors are susceptible to developing multiple organ failure (MOF), which is thought to be caused, at least in part, by excessive or maladaptive activation of inflammatory pathways. We previously demonstrated in rodents that T/HS results in liver injury that can be prevented by IL-6 administration at the start of resuscitation; however, the contribution of the severity of HS to the extent of liver injury, whether or not resuscitation is required, and the mechanism(s) for the IL-6 protective effect have not been reported. In the experiments described here, we demonstrated that the extent of liver inflammation induced by T/HS depends on the duration of hypotension and requires resuscitation. We established that IL-6 administration at the start of resuscitation is capable of completely reversing liver inflammation and is associated with increased Stat3 activation. Global assessment of the livers showed that the main effect of IL-6 was to normalize the T/HS-induced inflammation transcriptome. Pharmacological inhibition of Stat3 activity within the liver blocked the ability of IL-6 to prevent liver inflammation and to normalize the T/HS-induced liver inflammation transcriptome. Genetic deletion of a Stat3β, a naturally occurring, dominant-negative isoform of the Stat3, attenuated T/HS-induced liver inflammation, confirming a role for Stat3, especially Stat3α, in preventing T/HS-mediated liver inflammation. Thus, T/HS-induced liver inflammation depends on the duration of hypotension and requires resuscitation; IL-6 administration at the start of resuscitation reverses T/HS-induced liver inflammation, through activation of Stat3α, which normalized the T/HS-induced liver inflammation transcriptome
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