2,801 research outputs found
Assessment of Treatment Response after Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) for Appendiceal Peritoneal Metastases
Background The aim of this study was to analyse survival and surrogates for oncological response after PIPAC for appendiceal tumours. Methods This retrospective cohort study included consecutive patients with appendiceal peritoneal metastases (PM) treated in experienced PIPAC centers. Primary outcome measure was overall survival (OS) from the date of diagnosis of PM and from the start of PIPAC. Predefined secondary outcome included radiological response (RECIST criteria), repeat laparoscopy and peritoneal cancer index (PCI), histological response assessed by the Peritoneal regression grading system (PRGS) and clinical response. Results Final analysis included 77 consecutive patients (208 PIPAC procedures) from 15 centres. Median OS was 30 months (23.00–46.00) from time of diagnosis and 19 months (13.00–28.00) from start of PIPAC. 35/77 patients (45%) had ≥3 procedures (pp: per protocol). Objective response at PIPAC3 was as follows: RECIST: complete response 4 (11.4%), 11 (31.4%) partial/stable; mean PRGS at PIPAC3: 1.8 ± 0.9. Median PCI: 21 (IQR 18–27) vs. 22 (IQR 17–28) at baseline (p = 0.59); 21 (60%) and 18 (51%) patients were symptomatic at baseline and PIPAC3, respectively (p = 0.873). Median OS in the pp cohort was 22.00 months (19.00–NA) from 1st PIPAC. Conclusion Patients with PM of appendiceal origin had objective treatment response after PIPAC and encouraging survival curves call for further prospective evaluation
A diagnostic study on heat sources and moisture sinks in the monsoon trough area during active-break phases of the Indian summer monsoon, 1979
The diabatic heating over the Indian monsoon trough area, along with its thermal structure are studied for the 1979 summer monsoon based on FGGE level-IIIb upper air data of the European Centre for Medium Range Weather Forecasts. The apparent heat source and the apparent moisture sink over the trough area varied coherently with the rainfall over central India. The spatial and temporal variations of the vertically integrated apparent heat source and moisture sink were found to be coincident. These coincidences suggested that diabatic heating was largely contributed by the latent heat released by cumulus convection. During the active periods, the vertical structure of spatially-averaged heating and drying rates above the monsoon trough area showed higher values, as much as 8 K to 11 K day-1, at the mid-tropospheric level (500hPa), but much smaller and even negative values during break periods. Analyses of the heating and drying rates at 500 hPa level in a x-t diagram revealed that heat sources and moisture sinks propagated westward across the trough area with a period of 10-15 days (often called monsoon mode). The 30-50 day period of fluctuations showed a close link with the two major active/break phases of monsoon during the season. The monsoon mode became a part of the mid-season fluctuation of monsoon activity between the two major active phases. This paper discusses the spatial distribution of rainfall and heat source and moisture sink over the trough area, and the role of east-west differential heating in the development of weak/break phases of Indian summer monsoon 1979
Blood levels of adiponectin and IL-1Ra distinguish type 3c from type 2 diabetes: Implications for earlier pancreatic cancer detection in new-onset diabetes
BACKGROUND: Screening for pancreatic ductal adenocarcinoma (PDAC) in populations at high risk is recommended. Individuals with new-onset type 2 diabetes mellitus (NOD) are the largest high-risk group for PDAC. To facilitate screening, we sought biomarkers capable of stratifying NOD subjects into those with type 2 diabetes mellitus (T2DM) and those with the less prevalent PDAC-related diabetes (PDAC-DM), a form of type 3c DM commonly misdiagnosed as T2DM. METHODS: Using mass spectrometry- and immunoassay-based methodologies in a multi-stage analysis of independent sample sets (n=443 samples), blood levels of 264 proteins were considered using Ingenuity Pathway Analysis, literature review and targeted training and validation. FINDINGS: Of 30 candidate biomarkers evaluated in up to four independent patient sets, 12 showed statistically significant differences in levels between PDAC-DM and T2DM. The combination of adiponectin and interleukin-1 receptor antagonist (IL-1Ra) showed strong diagnostic potential, (AUC of 0.91; 95% CI: 0.84-0.99) for the distinction of T3cDM from T2DM. INTERPRETATION: Adiponectin and IL-1Ra warrant further consideration for use in screening for PDAC in individuals newly-diagnosed with T2DM. FUNDING: North West Cancer Research, UK, Cancer Research UK, Pancreatic Cancer Action, UK
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Retrospective model-based inference guides model-free credit assignment
An extensive reinforcement learning literature shows that organisms assign credit efficiently, even under conditions of state uncertainty. However, little is known about credit-assignment when state uncertainty is subsequently resolved. Here, we address this problem within the framework of an interaction between model-free (MF) and model-based (MB) control systems. We present and support experimentally a theory of MB retrospective-inference. Within this framework, a MB system resolves uncertainty that prevailed when actions were taken thus guiding an MF credit-assignment. Using a task in which there was initial uncertainty about the lotteries that were chosen, we found that when participants’ momentary uncertainty about which lottery had generated an outcome was resolved by provision of subsequent information, participants preferentially assigned credit within a MF system to the lottery they retrospectively inferred was responsible for this outcome. These findings extend our knowledge about the range of MB functions and the scope of system interactions
Phenomenological Implications of Deflected Mirage Mediation: Comparison with Mirage Mediation
We compare the collider phenomenology of mirage mediation and deflected
mirage mediation, which are two recently proposed "mixed" supersymmetry
breaking scenarios motivated from string compactifications. The scenarios
differ in that deflected mirage mediation includes contributions from gauge
mediation in addition to the contributions from gravity mediation and anomaly
mediation also present in mirage mediation. The threshold effects from gauge
mediation can drastically alter the low energy spectrum from that of pure
mirage mediation models, resulting in some cases in a squeezed gaugino spectrum
and a gluino that is much lighter than other colored superpartners. We provide
several benchmark deflected mirage mediation models and construct model lines
as a function of the gauge mediation contributions, and discuss their discovery
potential at the LHC.Comment: 29 pages, 9 figure
Thermodynamics of a class of non-asymptotically flat black holes in Einstein-Maxwell-Dilaton theory
We analyse in detail the thermodynamics in the canonical and grand canonical
ensembles of a class of non-asymptotically flat black holes of the
Einstein-(anti) Maxwell-(anti) Dilaton theory in 4D with spherical symmetry. We
present the first law of thermodynamics, the thermodynamic analysis of the
system through the geometrothermodynamics methods, Weinhold, Ruppeiner,
Liu-Lu-Luo-Shao and the most common, that made by the specific heat. The
geometric methods show a curvature scalar identically zero, which is
incompatible with the results of the analysis made by the non null specific
heat, which shows that the system is thermodynamically interacting, does not
possess extreme case nor phase transition. We also analyse the local and global
stability of the thermodynamic system, and obtain a local and global stability
for the normal case for 0<\gamma<1 and for other values of \gamma, an unstable
system. The solution where \gamma=0 separates the class of locally and globally
stable solutions from the unstable ones.Comment: 18 pages, version accepted for publication in General Relativity and
Gravitatio
Visual parameter optimisation for biomedical image processing
Background: Biomedical image processing methods require users to optimise input parameters to ensure high quality
output. This presents two challenges. First, it is difficult to optimise multiple input parameters for multiple
input images. Second, it is difficult to achieve an understanding of underlying algorithms, in particular, relationships
between input and output.
Results: We present a visualisation method that transforms users’ ability to understand algorithm behaviour by
integrating input and output, and by supporting exploration of their relationships. We discuss its application to a
colour deconvolution technique for stained histology images and show how it enabled a domain expert to
identify suitable parameter values for the deconvolution of two types of images, and metrics to quantify
deconvolution performance. It also enabled a breakthrough in understanding by invalidating an underlying
assumption about the algorithm.
Conclusions: The visualisation method presented here provides analysis capability for multiple inputs and outputs
in biomedical image processing that is not supported by previous analysis software. The analysis supported by our
method is not feasible with conventional trial-and-error approaches
Enriching rare variants using family-specific linkage information
Genome-wide association studies have been successful in identifying common variants for common complex traits in recent years. However, common variants have generally failed to explain substantial proportions of the trait heritabilities. Rare variants, structural variations, and gene-gene and gene-environment interactions, among others, have been suggested as potential sources of the so-called missing heritability. With the advent of exome-wide and whole-genome next-generation sequencing technologies, finding rare variants in functionally important sites (e.g., protein-coding regions) becomes feasible. We investigate the role of linkage information to select families enriched for rare variants using the simulated Genetic Analysis Workshop 17 data. In each replicate of simulated phenotypes Q1 and Q2 on 697 subjects in 8 extended pedigrees, we select one pedigree with the largest family-specific LOD score. Across all 200 replications, we compare the probability that rare causal alleles will be carried in the selected pedigree versus a randomly chosen pedigree. One example of successful enrichment was exhibited for gene VEGFC. The causal variant had minor allele frequency of 0.0717% in the simulated unrelated individuals and explained about 0.1% of the phenotypic variance. However, it explained 7.9% of the phenotypic variance in the eight simulated pedigrees and 23.8% in the family that carried the minor allele. The carrier’s family was selected in all 200 replications. Thus our results show that family-specific linkage information is useful for selecting families for sequencing, thus ensuring that rare functional variants are segregating in the sequencing samples
Small-Group Learning in an Upper-Level University Biology Class Enhances Academic Performance and Student Attitudes Toward Group Work
To improve science learning, science educators' teaching tools need to address two major criteria: teaching practice should mirror our current understanding of the learning process; and science teaching should reflect scientific practice. We designed a small-group learning (SGL) model for a fourth year university neurobiology course using these criteria and studied student achievement and attitude in five course sections encompassing the transition from individual work-based to SGL course design. All students completed daily quizzes/assignments involving analysis of scientific data and the development of scientific models. Students in individual work-based (Individualistic) sections usually worked independently on these assignments, whereas SGL students completed assignments in permanent groups of six. SGL students had significantly higher final exam grades than Individualistic students. The transition to the SGL model was marked by a notable increase in 10th percentile exam grade (Individualistic: 47.5%; Initial SGL: 60%; Refined SGL: 65%), suggesting SGL enhanced achievement among the least prepared students. We also studied student achievement on paired quizzes: quizzes were first completed individually and submitted, and then completed as a group and submitted. The group quiz grade was higher than the individual quiz grade of the highest achiever in each group over the term. All students – even term high achievers –could benefit from the SGL environment. Additionally, entrance and exit surveys demonstrated student attitudes toward SGL were more positive at the end of the Refined SGL course. We assert that SGL is uniquely-positioned to promote effective learning in the science classroom
Multiphase modelling of tumour growth and extracellular matrix interaction: mathematical tools and applications
Resorting to a multiphase modelling framework, tumours are described here as a mixture of tumour and host cells within a porous structure constituted by a remodelling extracellular matrix (ECM), which is wet by a physiological extracellular fluid. The model presented in this article focuses mainly on the description of mechanical interactions of the growing tumour with the host tissue, their influence on tumour growth, and the attachment/detachment mechanisms between cells and ECM. Starting from some recent experimental evidences, we propose to describe the interaction forces involving the extracellular matrix via some concepts coming from viscoplasticity. We then apply the model to the description of the growth of tumour cords and the formation of fibrosis
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