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1
Jacobs, H., J. Iacomini, M. van de Ven, S. Tonegawa, and A. Berns. "Domains of the TCR beta-chain required for early thymocyte development." Journal of Experimental Medicine 184, no. 5 (November 1, 1996): 1833–43. http://dx.doi.org/10.1084/jem.184.5.1833.
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The T cell receptor beta (TCR beta) chain controls the developmental transition from CD4-CD8- to CD4+8+thymocytes. We show that the extracellular constant region and the transmembrane region, but not the variable domain or cytoplasmic tail of the TCR beta chain are required for this differentiation step. TCR beta mutant chains lacking the cytoplasmic tail can be found at the cell surface both in functional TCR/CD3 complexes and in a GPI-anchored monomeric form indicating that the cytoplasmic tail of the TCR beta chain functions as an ER retention signal. The concordance between cell surface expression of the mutant chains as TCR/CD3 complexes and their capacity to mediate thymocyte differentiation supports the CD3 mediated feedback model in which preTCR/CD3 complexes control the developmental transition from CD4-CD8- to CD4+CD8+thymocytes.
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Ramm, Till, Emily J. Roycroft, and Johannes Müller. "Convergent evolution of tail spines in squamate reptiles driven by microhabitat use." Biology Letters 16, no. 2 (February 2020): 20190848. http://dx.doi.org/10.1098/rsbl.2019.0848.
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The repeated evolution of convergent or analogous traits is often used as evidence for adaptive evolution. Squamate reptiles show a high degree of convergence in a variety of morphological traits; however, the evolutionary mechanisms driving these patterns are not fully understood. Here, we investigate the evolution of tail spines, a trait that evolved multiple times in evolutionarily independent clades of lizards. Taking a comparative phylogenetic approach, we use 2877 squamate species to demonstrate that the evolution of spiny tails is correlated with microhabitat use, with species that live in rocky habitats significantly more likely to have evolved spiny tails. In the light of previous behavioural observations, our results suggest that spiny-tailed lizards have an advantage in rocky habitats through predation avoidance, where tail spines are used to prevent extraction from rocky crevices. In concordance with previous research on lizard body armour, our results suggest that the evolution of tail spines is coupled to both a rock-dwelling lifestyle and predator avoidance strategies, and highlight a complex interplay between different selective pressures on the evolution of defensive morphologies in reptiles.
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Cunha, César, Mariela Fernández, Jesús E. García, Verónica Andrea González-López, and Nícolas Romano. "A copula-based consistency analysis of education indicators." 4open 2 (2019): 19. http://dx.doi.org/10.1051/fopen/2019013.
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In this paper we investigate the consistency of quality indicators of the Brazilian public educational system. According to the newspaper Estado de São Paulo – Brazil, of January 18, 2017, only 7.3% of students in the third year of high school have an adequate level of mathematics, this shows the relevance of the evaluation and assessment of the Brazilian educational system. In this paper we explore the dependence between two indicators: (i) mean value between the proportions (in two subjects: Portuguese and Mathematics) of students under the basic level (SARESP classification) and (ii) rate of fails, during the years 2013, 2014 and 2015. (i) and (ii) are bases to define the educational quality of public schools for the population of young people, between 14 and 17 years old. This inspection is carried out through the Bayesian estimation of the parameters of the Asymmetric Cubic Sections (ACS) copula. We show that the dependence profile, year after year, behaves in a very unstable way, although during those years there were no substantial changes which justify such instability. Through the copula we compute conditional probabilities of tail events. We verify that an inversion occurred in the concordance/discordance between (i) and (ii). We compute the probability of (i) assuming high values, conditioned to a threshold in (ii). In 2013, as the threshold in (ii) increases the probability increases (concordance), in 2014 the threshold in (ii) is almost irrelevant to the probability and in 2015, as the threshold in (ii) increases the probability decreases (discordance). The inspection of the tail dependence allows to expose some kind of manipulation, in view of for instance, the maintenance of a global index índice de desenvolvimento da educação de São Paulo (IDESP) used to classify the educational institutions.
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Shan, Wei, Chen Liu, and Jing Yu. "FEATURES OF THE DISCIPLINE KNOWLEDGE NETWORK: EVIDENCE FROM CHINA." Technological and Economic Development of Economy 20, no. 1 (January 28, 2014): 45–64. http://dx.doi.org/10.3846/20294913.2014.825460.
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Interdisciplinary knowledge exchange constitutes a network with discipline nodes and knowledge flow edges. Using data on Chinese academic literature, the current paper establishes a discipline knowledge network and analyses its structural features. Citation analysis is first used to measure the flow of knowledge between disciplines to build a discipline knowledge network. Subsequently, the features of the network, such as degree distribution, degree correlation, knowledge flow mode and other structure properties, are then analysed based on complex networks and social network theory. The tail of the degree distribution of this discipline knowledge network is in concordance with exponential distribution. The network has also a distinct hierarchical structure. Moreover, the knowledge flow between disciplines is directional. It flows from certain basic and academic disciplines to the applied disciplines.
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Ben Othman, Mahmoud, Junkyu Han, Abdelfatteh El Omri, Riadh Ksouri, Mohamed Neffati, and Hiroko Isoda. "Antistress Effects of the Ethanolic Extract fromCymbopogon schoenanthusGrowing Wild in Tunisia." Evidence-Based Complementary and Alternative Medicine 2013 (2013): 1–9. http://dx.doi.org/10.1155/2013/737401.
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This study aimed to investigate the antistress properties of the ethanol extract ofCymbopogon schoenanthus(CSEE), growing wild in the southern part of Tunisia. The effect of extracts on H2O2-induced cytotoxicity and stress in human neuroblastoma SH-SY5Y cells. Its effect on stress-induced in ICR mice was exposed to force swim and tail suspension, in concordance with heat shock protein expression (HSP27 and HSP90), corticosterone, and catecholamine neurotransmitters level. Our results demonstrated that pretreatment of SH-SY5Y cells with CSEE at 1/2000, 1/1000, and 1/500 v/v dilutions significantly inversed H2O2-induced neurotoxicity. Moreover, CSEE treatments significantly reversed heat shock protein expression in heat-stressed HSP47-transformed cells (42°C, for 90 min) and mRNA expression of HSP27 and HSP90 in H2O2-treated SH-SY5Y. Daily oral administration of 100 mg/kg and 200 mg/kg CSEE was conducted to ICR mice for 2 weeks. It was resulted in a significant decrease of immobility time in forced swimming and tail suspension tests. The effect of CSEE on animal behavior was concordant with a significant regulation of blood serum corticosterone and cerebral cortex levels of catecholamine (dopamine, adrenaline, and noradrenaline). Therefore, this study was attempted to demonstrate the preventive potential of CSEE against stress disorders atin vitroandin vivolevels.
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Aldhufairi, Fadal Abdullah-A., Ranadeera G. M. Samanthi, and Jungsywan H. Sepanski. "New Families of Bivariate Copulas via Unit Lomax Distortion." Risks 8, no. 4 (October 14, 2020): 106. http://dx.doi.org/10.3390/risks8040106.
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This article studies a new family of bivariate copulas constructed using the unit-Lomax distortion derived from a transformation of the non-negative Lomax random variable into a variable whose support is the unit interval. Existing copulas play the role of the base copulas that are distorted into new families of copulas with additional parameters, allowing more flexibility and better fit to data. We present general forms for the new bivariate copula function and its conditional and density distributions. The properties of the new family of the unit-Lomax induced copulas, including the tail behaviors, limiting cases in parameters, Kendall’s tau, and concordance order, are investigated for cases when the base copulas are Archimedean, such as the Clayton, Gumbel, and Frank copulas. An empirical application of the proposed copula model is presented. The unit-Lomax distorted copula models outperform the base copulas.
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Ramachandran, A. V., R. V. Kinariwala, and R. V. Shah. "Haematopoiesis and Regeneration: Changes in the Liver, Spleen, Bone Marrow and Hepatic Iron Content during Tail Regeneration in the Scincid Lizard, Mabuya Carinata (Boulenger)." Amphibia-Reptilia 6, no. 4 (1985): 377–86. http://dx.doi.org/10.1163/156853885x00362.
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AbstractIn response to the observed changes in blood during tail regeneration, a detailed histophysiological study of the haemopoietic organs such as liver, spleen and bone marrow was undertaken. During regeneration, all three organs were found to undergo histophysiological changes. Increased haemopoietic activity in the marrow and hyperplasia of the white pulp were the important changes shown by the bone marrow and spleen respectively. In the liver, the most marked effect appeared to be the formation of large numbers of lymphocytopoietic nodules. Another interesting observation was the influx and destruction of red blood cells both in the liver and spleen, once during the early regressive phase and once during the late progressive phase of regeneration. An attempt is made to correlate these changes in the three haemopoietic organs with the possible involvement of lymphocytes in the formation of a regeneration blastema and a possible haemoglobin transition during regeneration. The present observations are in concordance with the previous observations on blood.
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Cole, David E. C., Francisco H. J. Yun, Betty Y. L. Wong, Andrew Y. Shuen, Ronald A. Booth, Alfredo Scillitani, Svetlana Pidasheva, Xiang Zhou, Lucie Canaff, and Geoffrey N. Hendy. "Calcium-sensing receptor mutations and denaturing high performance liquid chromatography." Journal of Molecular Endocrinology 42, no. 4 (January 29, 2009): 331–39. http://dx.doi.org/10.1677/jme-08-0164.
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The calcium-sensing receptor (CASR), a plasma membrane G-protein-coupled receptor, is expressed in parathyroid gland and kidney, and controls systemic calcium homeostasis. Inactivating CASR mutations are associated with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism, and activating mutations cause autosomal dominant hypocalcemia (ADH). CASR mutation identification plays an important role in the clinical management of mineral metabolism disorders. We describe here a high-throughput method using screening with denaturing high performance liquid chromatography (DHPLC) to initially interrogate 12 amplicons covering translated exons and exon/intron boundaries, followed by sequencing of any amplicon with a modified melting curve relative to wild type, and direct sequencing of a 13th amplicon encoding the COOH-terminal tail to distinguish causative mutations from three common missense single nucleotide polymorphisms. A blinded analysis of 32 positive controls representing mutations throughout the CASR sequence, as well as 22 negative controls, yielded a concordance rate of 100%. We report eight novel and five recurrent FHH mutations, along with six novel and two recurrent ADH mutations. Thus, DHPLC provides a rapid and effective means to screen for CASR mutations.
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Prabha, K. Radha Raja, and A. Sathish Selvakumar. "A clinico-epidemiological study of HIV seroconcordant and serodiscordant couples." International Journal of Research in Dermatology 5, no. 1 (January 25, 2019): 72. http://dx.doi.org/10.18203/issn.2455-4529.intjresdermatol20185129.
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<p class="abstract"><strong>Background:</strong> The aim of the present study was to assess the epidemiological and risk factors that are likely to influence HIV transmission among married couples and to study the pattern of sexually transmitted infections among both concordant and discordant HIV infected couples..</p><p class="abstract"><strong>Methods:</strong> This cross-sectional study was done on 100 HIV patients and their married partners attending to Institute of Venereology, Madras Medical College, Tamil Nadu. Detailed history of their high risk sexual behaviour, previous veneral diseases (PVDs) was noted and physical and genital examination was done. All the partners of HIV cases were examined for HIV to know the serostatus (seroconcordant and serodiscordant).<strong></strong></p><p class="abstract"><strong>Results:</strong> Among the 100 married couples, 65 couples were seroconcordant for HIV and 35 couples were serodiscordant. Of them, 94 males and 71 females were positive for HIV. History of PVDs was found in 34 patients (28 were seroconcordants and 6 were serodiscordants). The most common STD in the males noticed was ano-genital warts (n=11) and genital ulceration (n=11) is associated with maximum seroconcordance rates. Whereas in the females it was bacterial vaginosis (n=11).</p><p class="abstract"><strong>Conclusions:</strong> The findings suggest that risk factors such as STDs, PVDs in males, anal intercourse, sexual contact during menstruation, avoidance of condom during sexual act and lack of circumcision was significantly associated with presence of HIV concordance in the study population. Duration and frequency of sexual contact with partner, previous venereal diseases in females and ART were found not to influence the transmission of HIV.</p>
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Cherny, Nathan I., Elisabeth G. E. de Vries, Urania Dafni, Elizabeth Garrett-Mayer, Shannon E. McKernin, Martine Piccart, Nicola J. Latino, et al. "Comparative Assessment of Clinical Benefit Using the ESMO-Magnitude of Clinical Benefit Scale Version 1.1 and the ASCO Value Framework Net Health Benefit Score." Journal of Clinical Oncology 37, no. 4 (February 1, 2019): 336–49. http://dx.doi.org/10.1200/jco.18.00729.
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PURPOSE To better understand the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) and the ASCO Value Framework Net Health Benefit score version 2 (ASCO-NHB v2), ESMO and ASCO collaborated to evaluate the concordance between the frameworks when used to assess clinical benefit attributable to new therapies. METHODS The 102 randomized controlled trials in the noncurative setting already evaluated in the field testing of ESMO-MCBS v1.1 were scored using ASCO-NHB v2 by its developers. Measures of agreement between the frameworks were calculated and receiver operating characteristic curves used to define thresholds for the ASCO-NHB v2 corresponding to ESMO-MCBS v1.1 categories. Studies with discordant scoring were identified and evaluated to understand the reasons for discordance. RESULTS The correlation of the 102 pairs of scores for studies in the noncurative setting is estimated to be 0.68 (Spearman’s rank correlation coefficient; overall survival, 0.71; progression-free survival, 0.67). Receiver operating characteristic curves identified thresholds for ASCO-NHB v2 for facilitating comparisons with ESMO-MCBS v1.1 categories. After applying pragmatic threshold scores of 40 or less (ASCO-NHB v2) and 2 or less (ESMO-MCBS v1.1) for low benefit and 45 or greater (ASCO-NHB v2) and 4 to 5 (ESMO-MCBS v1.1) for substantial benefit, 37 discordant studies were identified. Major factors that contributed to discordance were different approaches to evaluation of relative and absolute gain for overall survival and progression-free survival, crediting tail of the curve gains, and assessing toxicity. CONCLUSION The agreement between the frameworks was higher than observed in other studies that sought to compare them. The factors that contributed to discordant scores suggest potential approaches to improve convergence between the scales.
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Šturm, Martina Burnik, Steve Smith, Oyunsaikhan Ganbaatar, Bayarbaatar Buuveibaatar, Boglarka Balint, John C. Payne, Christian C. Voigt, and Petra Kaczensky. "Isotope analysis combined with DNA barcoding provide new insights into the dietary niche of khulan in the Mongolian Gobi." PLOS ONE 16, no. 3 (March 29, 2021): e0248294. http://dx.doi.org/10.1371/journal.pone.0248294.
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With increasing livestock numbers, competition and avoidance are increasingly shaping resource availability for wild ungulates. Shifts in the dietary niche of wild ungulates are likely and can be expected to negatively affect their fitness. The Mongolian Gobi constitutes the largest remaining refuge for several threatened ungulates, but unprecedentedly high livestock numbers are sparking growing concerns over rangeland health and impacts on threatened ungulates like the Asiatic wild ass (khulan). Previous stable isotope analysis of khulan tail hair from the Dzungarian Gobi suggested that they graze in summer but switch to a poorer mixed C3 grass / C4 shrub diet in winter, most likely in reaction to local herders and their livestock. Here we attempt to validate these findings with a different methodology, DNA metabarcoding. Further, we extend the scope of the original study to the South Gobi Region, where we expect higher proportions of low-quality browse in the khulan winter diet due to a higher human and livestock presence. Barcoding confirmed the assumptions behind the seasonal diet change observed in the Dzungarian Gobi isotope data, and new isotope analysis revealed a strong seasonal pattern and higher C4 plant intake in the South Gobi Region, in line with our expectations. However, DNA barcoding revealed C4 domination of winter diet was due to C4 grasses (rather than shrubs) for the South Gobi Region. Slight climatic differences result in regional shifts in the occurrence of C3 and C4 grasses and shrubs, which do not allow for an isotopic separation along the grazer-browser continuum over the entire Gobi. Our findings do not allow us to confirm human impacts upon dietary preferences in khulan as we lack seasonal samples from the South Gobi Region. However, these data provide novel insight into khulan diet, raise new questions about plant availability versus preference, and provide a cautionary tale about indirect analysis methods if used in isolation or extrapolated to the landscape level. Good concordance between relative read abundance of C4 genera from barcoding and proportion of C4 plants from isotope analysis adds to a growing body of evidence that barcoding is a promising quantitative tool to understand resource partitioning in ungulates.
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Mazerolle, Daniel F., and Keith A. Hobson. "Estimating Origins of Short-Distance Migrant Songbirds in North America: Contrasting Inferences From Hydrogen Isotope Measurements of Feathers, Claws, and Blood." Condor 107, no. 2 (May 1, 2005): 280–88. http://dx.doi.org/10.1093/condor/107.2.280.
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Abstract Tracing movements of migratory birds between breeding and wintering areas is important for both theoretical and conservation purposes. Intrinsic markers such as stable isotopes have received considerable attention because of their usefulness for evaluating migratory connections without the need to mark and recapture individuals. Establishing migratory linkages using stable-isotope markers hinges on knowing which tissues most accurately reflect the isotopic signature of previous feeding locations of interest. Here, we assessed the correspondence among stable-hydrogen isotope (δD) values of feathers, claws, and cellular portions of blood from migrating White-throated Sparrows (Zonotrichia albicollis) to determine if these measures provided concordant estimates of origins. δD values of claws from birds captured during spring and fall migration were positively correlated with δD values of head feathers grown on the wintering grounds and tail feathers grown on breeding grounds, respectively, indicating that claws contained information on origins of individuals. However, analyses contrasting δD measurements of base and tip of claws, and head and tail feathers suggest that a significant amount of claw growth occurred during migration resulting in biased estimates of breeding and wintering origins. Thus, for ground-foraging birds like White-throated Sparrows, we caution against using isotope measurements of claws as long-term position indicators. δD values of blood were correlated with the δD values from the base of claws, which represented the most recent claw growth, but were not correlated with the δD values of claw tips and head feathers. Thus, it appears that the δD values of blood cells are not useful for estimating wintering latitudes of White-throated Sparrows captured during spring migration. Estimación de los Orígenes de las Aves Canoras Migratorias de Corta Distancia en América del Norte: Inferencias Contrastantes a Partir de Medidas de Isótopos de Hidrógeno de las Plumas, Garras y Sangre Resumen. El seguimiento de los movimientos de las aves migratorias entre las áreas reproductivas y de invernada es importante tanto por motivos teóricos como de conservación. Los marcadores intrínsecos como los isótopos estables han recibido una atención considerable debido a su utilidad para evaluar conexiones migratorias sin la necesidad de marcar y recapturar individuos. El establecimiento de vínculos migratorios usando marcadores de isótopos estables depende del conocimiento de cuáles son los tejidos que mejor reflejan la señal isotópica de los sitios de alimentación previos de interés. En este trabajo, evaluamos la relación entre los valores de los isótopos estables de hidrógeno (δD) de las plumas, garras y porciones celulares de la sangre de individuos migratorios de Zonotrichia albicollis para determinar si estas medidas brindaban estimaciones concordantes sobre sus lugares de origen. Los valores de δD de las garras de aves capturadas durante las migraciones de primavera y otoño estuvieron correlacionados positivamente con los valores de δD de las plumas de la cabeza desarrolladas en los sitios de invernada y de las plumas de la cola desarrolladas en los sitios reproductivos, indicando que las garras contenían información sobre los orígenes invernales de los individuos. Sin embargo, los análisis que contrastaron las medidas de δD de la base y la punta de las garras, y de las plumas de la cabeza y de la cola sugieren que una cantidad significativa del crecimiento de las garras ocurrió durante la migración, generando estimaciones sesgadas de los sitios reproductivos y de invernada de origen. De este modo, para las aves que se alimentan en el suelo como Z. albicollis, sugerimos no usar medidas de isótopos de las garras como indicadores a largo plazo de la posición. Los valores de δD de la sangre estuvieron correlacionados con los valores de δD de la base de las garras, los que reflejaron el crecimiento reciente de las garras, pero no estuvieron correlacionados con los valores de δD de la punta de la garras y de las plumas de la cabeza. De este modo, parece que los valores de δD de las células sanguíneas no son útiles para estimar las latitudes de invernada de individuos de Z. albicollis capturados durante la migración de primavera.
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Lock, Richard B., Kathryn Evans, Tara Pritchard, Cara Toscan, Chelsea Mayoh, Beverly Teicher, Raushan T. Kurmasheva, Peter J. Houghton, and Malcolm Smith. "A Single Mouse Trial Platform for Evaluation of Novel Agents in Acute Lymphoblastic Leukemia By the Pediatric Preclinical Testing Consortium." Blood 132, Supplement 1 (November 29, 2018): 4010. http://dx.doi.org/10.1182/blood-2018-99-113207.
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Abstract Introduction: While children diagnosed with the most common pediatric malignancy, acute lymphoblastic leukemia (ALL), now experience close to a 90% likelihood of cure, the outcome for several high-risk subtypes remains poor. Furthermore, since standard-of-care drugs are extremely effective in this disease, and there are relatively few patients eligible for early phase clinical trials, only the most promising new agents are advanced for clinical evaluation following rigorous preclinical testing. However, conventional preclinical testing of novel agents is not sufficiently resourced to be able to encompass the vast heterogeneity of pediatric ALL, and new approaches to preclinical testing are required in this disease. The purpose of this study was to evaluate the utility of a single mouse trial (SMT) platform for preclinical assessment of novel agents on an almost clinical trial scale, to encompass the broad heterogeneity of pediatric ALL in a single experiment, and to identify molecular biomarkers associated with in vivo drug responses when carried out using molecularly-annotated patient-derived xenografts (PDXs). Methods: Eighty pediatric ALL PDXs broadly representative of all pediatric ALL subtypes were characterized in terms of engraftment kinetics in immune-deficient NSG mice, and molecularly annotated by RNA-seq, exome-seq and DNA copy number analysis. Between 2-5 million cells from each PDX were inoculated via the tail vein into 2 NSG mice/PDX. Starting at 2 weeks post inoculation engraftment was monitored by flow cytometric enumeration of the proportion of human CD45+cells in the murine peripheral blood (%huCD45+). When the %huCD45+ for each PDX reached >1% one mouse/PDX was treated with the established drug and topoisomerase I inhibitor topotecan (Tpt, 0.6 mg/kg IP daily x 5 x 2 weeks, repeated at 21 days) and the other mouse was treated with the experimental drug and second mitochondria-derived activator of caspases (SMAC)-mimetic birinapant (Bpt, 15 mg/kg IP every 3 days x 5). Treatment response was monitored using stringent objective response criteria modeled after the clinical setting, by mouse event-free survival (EFS where an event was defined as 25% huCD45+), and by waterfall plots comparing the maximum decrease in %huCD45+at any point post treatment initiation. The authenticity of each PDX was verified using a 60-allele SNP array both at the time of inoculation and at relapse post drug treatment for all mice. Results: Retrospective analysis of 1,000 samples of "single mouse" data previously showed that the single mouse results predicted the overall group response from conventional testing 75.3% of the time, which increased to 94.3% if a deviation of ± one response category was allowed. SMT results were achieved for 71 (88.8%) and 73 (91.3%) of the intended 80 mice for Tpt and Bpt, respectively. Waterfall plots revealed that 60/71 (84.5%) and 30/73 (41.1%) of PDXs achieved regressions in response to Tpt and Bpt treatment, respectively. When compared with historical objective response measures from conventional drug testing carried out by the Pediatric Preclinical Testing Consortium (PPTC) the SMT results showed high concordance for both Tpt (R=0.904; P=0.014; n=7 PDXs) and Bpt (R=0.804; P<0.0001; n=20 PDXs). Moreover, the SMT confirmed the preferential in vivo efficacy of Bpt against B-ALL compared with T-ALL, early T-cell precursor ALL (ETP-ALL) and ALL with mixed linage leukemia gene rearrangements (MLLr-ALL) that was previously revealed by conventional testing carried out by the PPTC. Analysis of divergent responses observed within the MLLr-ALL subpanel (n=9 PDXs) to Tpt revealed a potential 40 gene signature model, with up-regulated genes in Responders being associated with transcription regulation, cellular proliferation and differentiation. Conclusions: This study has shown that SMTs provide an accurate and cost-effective platform for preclinical drug testing in pediatric ALL on an almost clinical trial scale. Moreover, SMTs can almost encompass the heterogeneity of pediatric ALL in a single experiment, and are likely to be useful for large-scale correlations with in vitro drug sensitivity data. Finally, SMTs have the power to identify molecular biomarkers of in vivo response to established and novel drugs in pediatric ALL when combined with exome-seq, RNA-seq and DNA copy number analysis of molecularly-annotated PDXs. Supported by U01CA199000 from the NCI. Disclosures No relevant conflicts of interest to declare.
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Roshania, Reshma P., Rukshan V. Mehta, Ashwini Shete, Rohini Bingewar, Sangeeta Kulkarni, Aprajit Mahajan, Grant Miller, Alessandro Tarozzi, and Reynaldo Martorell. "Agreement between dried blood spots and HemoCue in Tamil Nadu, India." Scientific Reports 11, no. 1 (April 29, 2021). http://dx.doi.org/10.1038/s41598-021-88425-y.
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AbstractIndia retains the world’s largest burden of anemia despite decades of economic growth and anemia prevention programming. Accurate screening and estimates of anemia prevalence are critical for successful anemia control. Evidence is mixed on the performance of HemoCue, a point-of-care testing device most widely used for large-scale surveys. The use of dried blood spots (DBS) to assess hemoglobin (Hb) concentration is a potential alternative, particularly in field settings. The objective of this study is to assess Hb measurement agreement between capillary HemoCue and DBS among two age groups, children 6–59 months and females age 12–40 years. We analyzed data from the baseline round of a cluster randomized rice fortification intervention in Cuddalore district of Tamil Nadu, India. Capillary blood was collected from a subset of participants for Hb assessment by HemoCue 301 and DBS methods. We calculated Lin’s concordance correlation coefficient, and tested bias by conducting paired t-tests of Hb concentration. Independence of the bias and Hb magnitude was examined visually using Bland–Altman plots and statistically tested by Pearson’s correlation. We assessed differences in anemia classification using McNemar’s test of marginal homogeneity. Concordance between HemoCue and DBS Hb measures was moderate for both children 6–59 months (ρc = 0.67; 95% CI 0.65, 0.71) and females 12–40 years (ρc = 0.67: 95% CI 0.64, 0.69). HemoCue measures were on average 0.06 g/dL higher than DBS for children (95% CI 0.002, 0.12; p = 0.043) and 0.29 g/dL lower than DBS for females (95% CI − 0.34, − 0.23; p < 0.0001). 50% and 56% of children were classified as anemic according to HemoCue and DBS, respectively (p < 0.0001). 55% and 47% of females were classified as anemic according to HemoCue and DBS, respectively (p < 0.0001). There is moderate statistical agreement of Hb concentration between HemoCue and DBS for both age groups. The choice of Hb assessment method has important implications for individual anemia diagnosis and population prevalence estimates. Further research is required to understand factors that influence the accuracy and reliability of DBS as a methodology for Hb assessment.
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Aldhufairi, Fadal A. A., and Jungsywan H. Sepanski. "New families of bivariate copulas via unit weibull distortion." Journal of Statistical Distributions and Applications 7, no. 1 (October 6, 2020). http://dx.doi.org/10.1186/s40488-020-00110-z.
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Abstract This paper introduces a new family of bivariate copulas constructed using a unit Weibull distortion. Existing copulas play the role of the base or initial copulas that are transformed or distorted into a new family of copulas with additional parameters, allowing more flexibility and better fit to data. We present a general form for the new bivariate copula function and its conditional and density distributions. The tail behaviors are investigated and indicate the unit Weibull distortion may result in new copulas with upper tail dependence when the base copula has no upper tail dependence. The concordance ordering and Kendall’s tau are derived for the cases when the base copulas are Archimedean, such as the Clayton and Frank copulas. The Loss-ALEA data are analyzed to evaluate the performance of the proposed new families of copulas.
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Pfuhler, Stefan, Ralph Pirow, Thomas R. Downs, Andrea Haase, Nicola Hewitt, Andreas Luch, Marion Merkel, et al. "Validation of the 3D reconstructed human skin Comet assay, an animal-free alternative for following-up positive results from standard in vitro genotoxicity assays." Mutagenesis, March 10, 2020. http://dx.doi.org/10.1093/mutage/geaa009.
Full textAbstract:
Abstract As part of the safety assessment process, all industrial sectors employ genotoxicity test batteries, starting with well-established in vitro assays. However, these batteries have limited predictive capacity for the in vivo situation, which may result in unnecessary follow-up in vivo testing or the loss of promising substances where animal tests are prohibited or not desired. To address this, a project involving regulators, academia and industry was established to develop and validate in vitro human skin-based genotoxicity assays for topically exposed substances, such as cosmetics ingredients. Here, we describe the validation of the 3D reconstructed skin (RS) Comet assay. In this multicenter study, chemicals were applied topically three times to the skin over 48 h. Isolated keratinocytes and fibroblasts were transferred to slides before electrophoresis and the resulting comet formation was recorded as % tail DNA. Before decoding, results of the validation exercise for 32 substances were evaluated by an independent statistician. There was a high predictive capacity of this assay when compared to in vivo outcomes, with a sensitivity of 77 (80)%, a specificity of 88 (97)% and an overall accuracy of 83 (92)%. The numbers reflect the calls of the performing laboratories in the coded phase, whereas those in parenthesis reflect calls according to the agreed evaluation criteria. Intra- and inter-laboratory reproducibility was also very good, with a concordance of 93 and 88%, respectively. These results generated with the Phenion® Full-Thickness skin model demonstrate its suitability for this assay, with reproducibly low background DNA damage and sufficient metabolic capacity to activate pro-mutagens. The validation outcome supports the use of the RS Comet assay to follow up positive results from standard in vitro genotoxicity assays when the expected route of exposure is dermal. Based on the available data, the assay was accepted recently into the OECD test guideline development program.