390 research outputs found
Spatial distribution and determinants of childhood vaccination refusal in the United States
Parental refusal and delay of childhood vaccination has increased in recent
years in the United States. This phenomenon challenges maintenance of herd
immunity and increases the risk of outbreaks of vaccine-preventable diseases.
We examine US county-level vaccine refusal for patients under five years of age
collected during the period 2012--2015 from an administrative healthcare
dataset. We model these data with a Bayesian zero-inflated negative binomial
regression model to capture social and political processes that are associated
with vaccine refusal, as well as factors that affect our measurement of vaccine
refusal.Our work highlights fine-scale socio-demographic characteristics
associated with vaccine refusal nationally, finds that spatial clustering in
refusal can be explained by such factors, and has the potential to aid in the
development of targeted public health strategies for optimizing vaccine uptake
Dallas with balls: televized sport, soap opera and male and female pleasures
Two of the most popular of television genres, soap opera and sports coverage have been very much differentiated along gender lines in terms of their audiences. Soap opera has been regarded very much as a 'gynocentric' genre with a large female viewing audience while the audiences for television sport have been predominantly male. Gender differentiation between the genres has had implications for the popular image of each. Soap opera has been perceived as inferior; as mere fantasy and escapism for women while television sports has been perceived as a legitimate, even edifying experience for men.
In this article the authors challenge the view that soap opera and television sport are radically different and argue that they are, in fact, very similar in a number of significant ways. They suggest that both genres invoke similar structures of feeling and sensibility in their respective audiences and that television sport is a 'male soap opera'. They consider the ways in which the viewing context of each genre is related to domestic life and leisure, the ways in which the textual structure and conventions of each genre invoke emotional identification, and finally, the ways in which both genres re-affirm gender identities
An automated fitting procedure and software for dose-response curves with multiphasic features.
In cancer pharmacology (and many other areas), most dose-response curves are satisfactorily described by a classical Hill equation (i.e. 4 parameters logistical). Nevertheless, there are instances where the marked presence of more than one point of inflection, or the presence of combined agonist and antagonist effects, prevents straight-forward modelling of the data via a standard Hill equation. Here we propose a modified model and automated fitting procedure to describe dose-response curves with multiphasic features. The resulting general model enables interpreting each phase of the dose-response as an independent dose-dependent process. We developed an algorithm which automatically generates and ranks dose-response models with varying degrees of multiphasic features. The algorithm was implemented in new freely available Dr Fit software (sourceforge.net/projects/drfit/). We show how our approach is successful in describing dose-response curves with multiphasic features. Additionally, we analysed a large cancer cell viability screen involving 11650 dose-response curves. Based on our algorithm, we found that 28% of cases were better described by a multiphasic model than by the Hill model. We thus provide a robust approach to fit dose-response curves with various degrees of complexity, which, together with the provided software implementation, should enable a wide audience to easily process their own data.This work was funded by Cancer Research UK grant C14303/A17197.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/srep1470
ATCT-35QUALITY OF LIFE, COGNITIVE FUNCTION AND FUNCTIONAL STATUS IN THE EF-14 TRIAL: A PROSPECTIVE, MULTI-CENTER TRIAL OF TTFIELDS WITH TEMOZOLOMIDE COMPARED TO TEMOZOLOMIDE ALONE IN PATIENTS WITH NEWLY DIAGNOSED GBM
Modelling of the cancer cell cycle as a tool for rational drug development: A systems pharmacology approach to cyclotherapy
The dynamic of cancer is intimately linked to a dysregulation of the cell cycle and signalling pathways. It has been argued that selectivity of treatments could exploit loss of checkpoint function in cancer cells, a concept termed "cyclotherapy". Quantitative approaches that describe these dysregulations can provide guidance in the design of novel or existing cancer therapies. We describe and illustrate this strategy via a mathematical model of the cell cycle that includes descriptions of the G1-S checkpoint and the spindle assembly checkpoint (SAC), the EGF signalling pathway and apoptosis. We incorporated sites of action of four drugs (palbociclib, gemcitabine, paclitaxel and actinomycin D) to illustrate potential applications of this approach. We show how drug effects on multiple cell populations can be simulated, facilitating simultaneous prediction of effects on normal and transformed cells. The consequences of aberrant signalling pathways or of altered expression of pro- or anti-apoptotic proteins can thus be compared. We suggest that this approach, particularly if used in conjunction with pharmacokinetic modelling, could be used to predict effects of specific oncogene expression patterns on drug response. The strategy could be used to search for synthetic lethality and optimise combination protocol designs
Interaction between Intrathecal Gabapentin and Adenosine in the Formalin Test of Rats
Spinal gabapentin and adenosine have been known to display an antinociceptive effect. We evaluated the nature of the interaction between gabapentin and adenosine in formalin-induced nociception at the spinal level. Male Sprague-Dawley rats were prepared for intrathecal catheterization. Pain was evoked by injection of formalin solution (5%, 50 µL) into the hindpaw. After examination of the effects of gabapentin and adenosine, the resulting interaction was investigated with isobolographic and fractional analyses. Neither gabapentin nor adenosine affected motor function. Gabapentin or adenosine decreased the sum of the number of flinches during phase 2, but not during phase 1 in the formalin test. Isobolographic analysis, in phase 2, revealed an additive interaction between gabapentin and adenosine. Taken together, intrathecal gabapentin and adenosine attenuated the facilitated state and interacted additively with each other
Characterisation of the substrate specificity of the nitrile hydrolyzing system of the acidotolerant black yeast Exophiala oligosperma R1
The `black yeast' Exophiala oligosperma R1 can utilise various
organic nitriles under acidic conditions as nitrogen sources. The induction of
a phenylacetonitrile converting activity was optimised by growing the strain
in the presence of different nitriles and /or complex or inorganic nitrogen
sources. The highest nitrile hydrolysing activity was observed with cells
grown with 2-cyanopyridine and NaNO3. The cells metabolised the
inducer and grew with 2-cyanopyridine as sole source of nitrogen. Cell
extracts converted various (substituted) benzonitriles and
phenylacetonitriles. They usually converted the isomers carrying a substituent
in the meta-position with higher relative activities than the
corresponding para- or ortho-substituted isomers. Aliphatic
substrates such as acrylonitrile and 2-hydroxy-3-butenenitrile were also
hydrolysed. The highest specific activity was detected with 4-cyanopyridine.
Most nitriles were almost exclusively converted to the corresponding acids and
no or only low amounts of the corresponding amides were formed. The cells
hydrolysed amides only with extremely low activities. It was therefore
concluded that the cells harboured a nitrilase activity. The specific
activities of whole cells and cell extracts were compared for different
nitriles and evidence obtained for limitation in the substrate-uptake by whole
cells. The conversion of 2-hydroxy-3-butenenitrile to 2-hydroxy-3-butenoic
acid at pH 4 demonstrated the unique ability of cells of E.
oligosperma R1 to hydrolyse aliphatic α-hydroxynitriles under
acidic conditions. The organism could grow with phenylacetonitrile as sole
source of carbon, energy and nitrogen. The degradation of phenylacetonitrile
presumably proceeds via phenylacetic acid, 2-hydroxyphenylacetic acid,
2,5-dihydroxyphenylacetic acid (homogentisate), maleylacetoacetate and
fumarylacetoacetate
Hepatic Radiofrequency Ablation Using Multiple Probes: Ex Vivo and In Vivo Comparative Studies of Monopolar versus Multipolar Modes
OBJECTIVE: We wanted to compare the efficiency of multipolar radiofrequency ablation (RFA) using three perfused-cooled electrodes with multiple overlapping and simultaneous monopolar techniques for creating an ablation zone in ex vivo bovine livers and in in vivo porcine livers.
MATERIALS AND METHODS: In the ex vivo experiments, we used a 200 W generator (Valleylab, CC-3 model) and three perfused-cooled electrodes or internally cooled electrodes to create 30 coagulation zones by performing consecutive monopolar RFA (group A, n = 10), simultaneous monopolar RFA (group B, n = 10) or multipolar RFA (group C, n = 10) in explanted bovine livers. In the consecutive mode, three ablation spheres were created by sequentially applying 150 watts radiofrequency (RF) energy to the internally cooled electrodes for 12 minutes each for a total of 36 minutes. In the simultaneous monopolar and multipolar modes, RF energy was concurrently applied to the three perfused-cooled electrodes for 20 minutes at 150 watt with instillation of 6% hypertonic saline at 2 mL/min. During RFA, we measured the temperatures of the treated area at its center. The changes in impedance, the current and liver temperature during RFA, as well as the dimensions of the thermal ablation zones, were compared among the three groups. In the in vivo experiments, three coagulations were created by performing multipolar RFA in a pig via laparotomy with using same parameter as the ex vivo study.
RESULTS: In the ex vivo experiments, the impedance was gradually decreased during the RFA in groups B and C, but in group A, the impedance was increased during RFA and this induced activation by the pulsed RF technique. In groups A, B and C, the mean final-temperature values were 80+/-10 degrees C, 69+/-18 degrees C and 79+/-12 degrees C, respectively (p < 0.05). The multipolar mode created a larger volume of ablation than did the other modes: 37.6+/-4.0 cm3 (group A); 44.9+/-12.7 cm3 (group B); and 78.9+/-6.9 cm3 (group C) (p < 0.05). In the in vivo experiment, the pig well tolerated the RFA procedure and no major complications occurred during the 4 days of the follow-up period. The mean volume of coagulations produced by multipolar RFA in the pig liver was 60.5+/-17.9 cm3.
CONCLUSION: For the multiple probe RFA, the multipolar mode with hypertonic saline instillation was more efficient in generating larger areas of thermal ablation than either the consecutive or simultaneous monopolar modes.ope
Improving parent satisfaction: an intervention to increase neonatal parent–provider communication
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