Parameter Inference in the Pulmonary Circulation of Mice

This study focuses on parameter inference in a pulmonary blood cir- culation model for mice. It utilises a fluid dynamics network model that takes selected parameter values and aims to mimic features of the pulmonary haemody- namics under normal physiological and pathological conditions. This is of medical relevance as it allows monitoring of the progression of pulmonary hypertension. Constraint nonlinear optimization is successfully used to learn the parameter values

An independently validated nomogram for isocitrate dehydrogenase-wild-type glioblastoma patient survival.

BackgroundIn 2016, the World Health Organization reclassified the definition of glioblastoma (GBM), dividing these tumors into isocitrate dehydrogenase (IDH)-wild-type and IDH-mutant GBM, where the vast majority of GBMs are IDH-wild-type. Nomograms are useful tools for individualized estimation of survival. This study aimed to develop and independently validate a nomogram for IDH-wild-type patients with newly diagnosed GBM.MethodsData were obtained from newly diagnosed GBM patients from the Ohio Brain Tumor Study (OBTS) and the University of California San Francisco (UCSF) for diagnosis years 2007-2017 with the following variables: age at diagnosis, sex, extent of resection, concurrent radiation/temozolomide (TMZ) status, Karnofsky Performance Status (KPS), O6-methylguanine-DNA methyltransferase (MGMT) methylation status, and IDH mutation status. Survival was assessed using Cox proportional hazards regression, random survival forests, and recursive partitioning analysis, with adjustment for known prognostic factors. The models were developed using the OBTS data and independently validated using the UCSF data. Models were internally validated using 10-fold cross-validation and externally validated by plotting calibration curves.ResultsA final nomogram was validated for IDH-wild-type newly diagnosed GBM. Factors that increased the probability of survival included younger age at diagnosis, female sex, having gross total resection, having concurrent radiation/TMZ, having a high KPS, and having MGMT methylation.ConclusionsA nomogram that calculates individualized survival probabilities for IDH-wild-type patients with newly diagnosed GBM could be useful to physicians for counseling patients regarding treatment decisions and optimizing therapeutic approaches. Free software for implementing this nomogram is provided: https://gcioffi.shinyapps.io/Nomogram_For_IDH_Wildtype_GBM_H_Gittleman/

Bioresorbable Polylactide Interbody Implants in an Ovine Anterior Cervical Discectomy and Fusion Model: Three-Year Results

Study Design. In vivo study of anterior discectomy and fusion using a bioresorbable 70:30 poly(l-lactide-co-d,l-lactide) interbody implant in an ovine model. Objective. To evaluate the efficacy of the polylactide implant to function as an interbody fusion device, and to assess the tissue reaction to the material during the resorption process. Summary of Background Data. The use of polylactide as a cervical interbody implant has several potential advantages when compared with traditional materials. Having an elastic modulus very similar to bone minimizes the potential for stress shielding, and as the material resorbs additional loading is transferred to the developing fusion mass. Although preclinical and clinical studies have demonstrated the suitability of polylactide implants for lumbar interbody fusion, detailed information on cervical anterior cervical discectomy and fusion (ACDF) with polylactide devices is desirable. Methods. Single level ACDF was performed in 8 skeletally mature ewes. Bioresorbable 70:30 poly (l-lactide-co-d,l-lactide) interbody implants packed with autograft were used with single-level metallic plates. Radiographs were made every 3 months up to 1 year, and yearly thereafter. The animals were killed at 6 months (3 animals), 12 months (3 animals), and 36 months (2 animals). In addition to the serial plain radiographs, the specimens were evaluated by nondestructive biomechanical testing and undecalcified histologic analysis. Results. The bioresorbable polylactide implants were effective in achieving interbody fusion. The 6-month animals appeared fused radiographically and biomechanically, whereas histologic sections demonstrated partial fusion (in 3 of 3 animals). Radiographic fusion was confirmed histologically and biomechanically at 12 months (3 of 3 animals) and 36 months (2 of 2 animals). A mild chronic inflammatory response to the resorbing polylactide implant was observed at both 6 months and 12 months. At 36 months, the operative levels were solidly fused and the implants were completely resorbed. No adverse tissue response was observed in any animal at any time period. Conclusion. Interbody fusion was achieved using bioresorbable polylactide implants, with no evidence of implant collapse, extrusion, or adverse tissue response to the material. The use of polylactide as a cervical interbody device appears both safe and effective based on these ACDF animal model results

Coarse-graining of cellular automata, emergence, and the predictability of complex systems

We study the predictability of emergent phenomena in complex systems. Using nearest neighbor, one-dimensional Cellular Automata (CA) as an example, we show how to construct local coarse-grained descriptions of CA in all classes of Wolfram's classification. The resulting coarse-grained CA that we construct are capable of emulating the large-scale behavior of the original systems without accounting for small-scale details. Several CA that can be coarse-grained by this construction are known to be universal Turing machines; they can emulate any CA or other computing devices and are therefore undecidable. We thus show that because in practice one only seeks coarse-grained information, complex physical systems can be predictable and even decidable at some level of description. The renormalization group flows that we construct induce a hierarchy of CA rules. This hierarchy agrees well with apparent rule complexity and is therefore a good candidate for a complexity measure and a classification method. Finally we argue that the large scale dynamics of CA can be very simple, at least when measured by the Kolmogorov complexity of the large scale update rule, and moreover exhibits a novel scaling law. We show that because of this large-scale simplicity, the probability of finding a coarse-grained description of CA approaches unity as one goes to increasingly coarser scales. We interpret this large scale simplicity as a pattern formation mechanism in which large scale patterns are forced upon the system by the simplicity of the rules that govern the large scale dynamics.Comment: 18 pages, 9 figure

Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma.

Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM). In the current study, ex vivo metabolic profiles of image-guided tissue samples obtained from patients with newly diagnosed and recurrent LGG were investigated using proton high-resolution magic angle spinning spectroscopy (1H HR-MAS). Distinct spectral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP. Levels of 2-hydroxyglutarate (2HG) were correlated with increased mitotic activity, axonal disruption, vascular neoplasia, and with several brain metabolites including the choline species, glutamate, glutathione, and GABA. The information obtained in this study may be used to develop strategies for in vivo characterization of infiltrative glioma, in order to improve disease stratification and to assist in monitoring response to therapy

On computational irreducibility and the predictability of complex physical systems

Using elementary cellular automata (CA) as an example, we show how to coarse-grain CA in all classes of Wolfram's classification. We find that computationally irreducible (CIR) physical processes can be predictable and even computationally reducible at a coarse-grained level of description. The resulting coarse-grained CA which we construct emulate the large-scale behavior of the original systems without accounting for small-scale details. At least one of the CA that can be coarse-grained is irreducible and known to be a universal Turing machine.Comment: 4 pages, 2 figures, to be published in PR

Pengendalian Biaya Dan Waktu Dengan Metode Analisis Nilai Dan Hasil Dengan Microsoft Project 2010 (Studi Kasus : Gedung Mantos Tahap III)

Pengendalian dalam proyek merupakan fungsi paling pokok dama pelaksanaan suatu proyek konstruksi. Pengendalian sebagai alat untuk membantu mengendalikan proyek, membantu pelaksanaan dan penyelesaian dalam suatu proyek konstruksi. Pelaksanaan suatu proyek umumnya sering terjadi penyimpanan – penyimpangan dimana biaya yang dikeluarkan dan jadwal yang direncanakan melampaui batas yang direncanakan. Pengendalian proyek bertujuan untuk mengendaliakn biaya dan waktu agar sesuai dengan biaya dan jadwal yang direncanakan. Metode nilai hasil merupakan pengembangan teknik pengendalian grafik S sampai mampu menganalisis varians biaya secara stimulant sehingga dapat melihat kemajuan proyek dari jadwal dengan anggaran yang telah dialokasikan. Metode nilai hasil ini mencakup rencana anggaran dan biaya (RAB), daftar harga satuan upah dan bahan, analisa harga satuan serta laporan kemajuan proyek di olah untuk mendapatkan BCWS (Budgeted Cost of Work Schedule), ACWP (Actual Cost of Work Performance) dan BCWP (Budgeted Cost of Work Performance) Dari hasil penerapan metode konsep nilai hasil diketahui sampai hasil tinjauan pada minggu ke 6 di dapatkan BCWS = Rp. 46,932,747,947.29; ACWP = Rp. 45,928,815,000.00; BCWP = Rp. 47,633,716,500.77; sedangkan varian biaya (CV) pada bulan satu sampai tiga adalah negative (-) dan pada bulan ke empat sampai akhir pelaksanaan proyek adalah positif (+) begitu pun varian jadwal. Dan dapat diketahui prakiraan biaya akhir proyek EAC (Estimate At Complection) adalah Rp. 70,829,440,000.00, dengan anggaran rencana sebesar Rp. 72,391,666,414.54. Estimate Complection Date (ECD) proyek mengalami sedikit kemajuan terhadap jadwal yang direncanakan yaitu 2 har

The Clumping Transition in Niche Competition: a Robust Critical Phenomenon

We show analytically and numerically that the appearance of lumps and gaps in the distribution of n competing species along a niche axis is a robust phenomenon whenever the finiteness of the niche space is taken into account. In this case depending if the niche width of the species $\sigma$ is above or below a threshold $\sigma_c$, which for large n coincides with 2/n, there are two different regimes. For $\sigma > sigma_c$ the lumpy pattern emerges directly from the dominant eigenvector of the competition matrix because its corresponding eigenvalue becomes negative. For $\sigma </- sigma_c$ the lumpy pattern disappears. Furthermore, this clumping transition exhibits critical slowing down as $\sigma$ is approached from above. We also find that the number of lumps of species vs. $\sigma$ displays a stair-step structure. The positions of these steps are distributed according to a power-law. It is thus straightforward to predict the number of groups that can be packed along a niche axis and it coincides with field measurements for a wide range of the model parameters.Comment: 16 pages, 7 figures; http://iopscience.iop.org/1742-5468/2010/05/P0500