What\u27s in The Bag?

As the bioprocessing industry continues to shift towards single-use systems, there is an increasing need for polymers with improved functionality. This article includes a review of the chemistry and functionality of various polymeric families, and a description of various tools that can be useful. Polyethylene resins are largely used in a variety of single use applications. This paper describes polyethylene chemistry in more detail so that single use system manufacturers and biopharmaceuticals manufacturers can optimize the use of polyethylene polymers in a particular application. The process in which the families of polyethylene polymer resins are manufactured dictates the degree of crystallinity, chain branching of the polymer, and migratory species. These molecular properties determine the physical properties (e.g. strength, flexibility, transparency, etc.) and the processability of the polymer in melt extrusion. The type of polymer can also determine the need for antioxidants and other processing additives which can affect the extractable profile of the contact layer. In addition to polyethylene resins, other polymeric families are known in the industry for providing specific functions such as barrier to moisture or gases, and adhesion. Polyamides, adhesive resins, and EVOH are very well known in the food packaging industry. Extending experience and leveraging tools from food packaging can benefit those who participate in the single use bioprocessing arena. Modeling tools can be used to optimize film structures, relative to cost, thickness, and performance, while minimizing the need for producing numerous test samples. Understanding the properties of the various polymer families allows for the design of the ideal solution for the targeted application(s)

A macroscopic model including membrane exchange for diffusion MRI

International audienceDiffusion Magnetic Resonance Imaging (dMRI) is a promising tool to obtain useful infor- mation on microscopic structure and has been extensively applied to biological tissues. We establish a new macroscopic model from homogenization theory to obtain the aggregate dMRI signal measured in practice in the case of intermediate water exchange across cellular membranes. Based on a particular scaling of the permeability condition modeling cellular membranes, this model accurately reproduces the memory effects observed in practice. Explicit formulae given by homogenization for the coeffcients of this model emphasize their link to the relevant physiological quantities, and the inverse problem of retrieving these coefficients from a realistic set of measurements is considered

Using Salomé to reproduce the structure and to observe the diffusion of water molecules in biological tissue

Poster for SALOME User Day 2012 on 20th of November 2012 on the premises of EDF R&D in Clamart.Diffusion magnetic resonance imaging (DMRI) can give useful information on cellular structure and its structural changes. Salomé is used to reproduce some complicated shapes in d-dimensions (d=2,3) that are used to represent the natural structures of various biological tissue. The meshes representing these shapes are used as inputs to a finite element code that we built upon FENICS C++. Results were obtained for a model of globlastoma (cerebral tumor) as a Voronoi diagram which was used to observe the convergence of the apparent diffusion tensor in long-time limit to the effective diffusion tensor computed by homogenization theory

New ODE Model for Diffusion MRI Signal

International audienceWater diffusion in biological tissues is not Gaussian and signal attenuation is not monoexponential with b-value [1]. Approaches to deal with this behavior include the bi-exponential model [1,2], the Karger model [3], and Kurtosis approach [4]. We formulate an ODE model for diffusion MRI signal that is more general than Karger model, valid for more general diffusion gradient shapes and gives a good approximation to the ADC and Kurtosis. Given DMRI signals before and after cell swelling, we can estimate the amount of cell swelling after numerically solving an ODE system

Numerical simulation of diffusion MRI signals using an adaptive time-stepping method

International audienceThe effect on the MRI signal of water diffusion in biological tissues in the presence of applied magnetic field gradient pulses can be modelled by a multiple compartment Bloch-Torrey partial differential equation. We present a method for the numerical solution of this equation by coupling a standard Cartesian spatial discretization with an adaptive time discretization. The time discretization is done using the explicit Runge-Kutta-Chebyshev method, which is more efficient than the forward Euler time discretization for diffusive-type problems. We use this approach to simulate the diffusion MRI signal from the extra-cylindrical compartment in a tissue model of the brain gray matter consisting of cylindrical and spherical cells and illustrate the effect of cell membrane permeability

Analytical and numerical study of the apparent diffusion coefficient in diffusion MRI at long diffusion times and low b-values

Diffusion magnetic resonance imaging provides a measure of the average distance travelled by water molecules in a medium and can give useful information on cellular structure and structural change when the medium is biological tissue. In this paper, two approximate models for the apparent diffusion coefficient at low b-values and long diffusion times are formulated and validated. The first is a steady-state partial differential equation model that gives the steady-state (infinite time) effective diffusion tensor for general cellular geometries. For nearly isotropic diffusion where the intra-cellular compartment consists of non-elongated cells, a second approximate model is provided in the form of analytical formulae for the eigenvalue of the steady-state effective diffusion tensor. Both models are validated by numerical simulations on a variety of cells sizes and shapes

Epigenetic Changes with Dietary Soy in Cynomolgus Monkeys

Nutritional interventions are important alternatives for reducing the prevalence of many chronic diseases. Soy is a good source of protein that contains isoflavones, including genistein and daidzein, and may alter the risk of obesity, Type 2 diabetes, osteoporosis, cardiovascular disease, and reproductive cancers. We have shown previously in nonhuman primates that soy protein containing isoflavones leads to improved body weight, insulin sensitivity, lipid profiles, and atherosclerosis compared to protein without soy isoflavones (casein), and does not increase the risk of cancer. Since genistein has been shown to alter DNA methylation, we compared the methylation profiles of cynomolgus monkeys, from multiple tissues, eating two high-fat, typical American diets (TAD) with similar macronutrient contents, with or without soy protein. DNA methylation status was successfully determined for 80.6% of the probes in at least one tissue using Illumina's HumanMethylation27 BeadChip. Overall methylation increased in liver and muscle tissue when monkeys switched from the TAD-soy to the TAD-casein diets. Genes involved in epigenetic processes, specifically homeobox genes (HOXA5, HOXA11, and HOXB1), and ABCG5 were among those that changed between diets. These data support the use of the HumanMethylation27 BeadChip in cynomolgus monkeys and identify epigenetic changes associated with dietary interventions with soy protein that may potentially affect the etiology of complex diseases

Comparative DNA methylome analysis of endometrial carcinoma reveals complex and distinct deregulation of cancer promoters and enhancers

BACKGROUND: Aberrant DNA methylation is a hallmark of many cancers. Classically there are two types of endometrial cancer, endometrioid adenocarcinoma (EAC), or Type I, and uterine papillary serous carcinoma (UPSC), or Type II. However, the whole genome DNA methylation changes in these two classical types of endometrial cancer is still unknown. RESULTS: Here we described complete genome-wide DNA methylome maps of EAC, UPSC, and normal endometrium by applying a combined strategy of methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme digestion sequencing (MRE-seq). We discovered distinct genome-wide DNA methylation patterns in EAC and UPSC: 27,009 and 15,676 recurrent differentially methylated regions (DMRs) were identified respectively, compared with normal endometrium. Over 80% of DMRs were in intergenic and intronic regions. The majority of these DMRs were not interrogated on the commonly used Infinium 450K array platform. Large-scale demethylation of chromosome X was detected in UPSC, accompanied by decreased XIST expression. Importantly, we discovered that the majority of the DMRs harbored promoter or enhancer functions and are specifically associated with genes related to uterine development and disease. Among these, abnormal methylation of transposable elements (TEs) may provide a novel mechanism to deregulate normal endometrium-specific enhancers derived from specific TEs. CONCLUSIONS: DNA methylation changes are an important signature of endometrial cancer and regulate gene expression by affecting not only proximal promoters but also distal enhancers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-868) contains supplementary material, which is available to authorized users

New Transmission Condition Accounting For Diffusion Anisotropy In Thin Layers Applied To Diffusion MRI

International audienceThe Bloch-Torrey Partial Differential Equation (PDE) can be used to model the diffusion Magnetic Resonance Imaging (dMRI) signal in biological tissue. In this paper, we derive an Anisotropic Diffusion Transmission Condition (ADTC) for the Bloch-Torrey PDE that accounts for anisotropic diffusion inside thin layers. Such diffusion occurs, for example, in the myelin sheath surrounding the axons of neurons. This ADTC can be interpreted as an asymptotic model of order two with respect to the layer thickness and accounts for water diffusion in the normal direction that is low compared to the tangential direction. We prove uniform stability of the asymptotic model with respect to the layer thickness and a mass conservation property. We demonstrate the quadratic accuracy of the ADTC by numerical tests and show that it gives a better approximation of the dMRI signal than a simple transmission condition that assumes isotropic diffusion in the layers

Delays in hospital admissions in patients with fractures across 18 low-income and middle-income countries (INORMUS): a prospective observational study

© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: The Lancet Commission on Global Surgery established the Three Delays framework, categorising delays in accessing timely surgical care into delays in seeking care (First Delay), reaching care (Second Delay), and receiving care (Third Delay). Globally, knowledge gaps regarding delays for fracture care, and the lack of large prospective studies informed the rationale for our international observational study. We investigated delays in hospital admission as a surrogate for accessing timely fracture care and explored factors associated with delayed hospital admission. Methods: In this prospective observational substudy of the ongoing International Orthopaedic Multicenter Study in Fracture Care (INORMUS), we enrolled patients with fracture across 49 hospitals in 18 low-income and middle-income countries, categorised into the regions of China, Africa, India, south and east Asia, and Latin America. Eligible patients were aged 18 years or older and had been admitted to a hospital within 3 months of sustaining an orthopaedic trauma. We collected demographic injury data and time to hospital admission. Our primary outcome was the number of patients with open and closed fractures who were delayed in their admission to a treating hospital. Delays for patients with open fractures were defined as being more than 2 h from the time of injury (in accordance with the Lancet Commission on Global Surgery) and for those with closed fractures as being a delay of more than 24 h. Secondary outcomes were reasons for delay for all patients with either open or closed fractures who were delayed for more than 24 h. We did logistic regression analyses to identify risk factors of delays of more than 2 h in patients with open fractures and delays of more than 24 h in patients with closed fractures. Logistic regressions were adjusted for region, age, employment, urban living, health insurance, interfacility referral, method of transportation, number of fractures, mechanism of injury, and fracture location. We further calculated adjusted relative risk (RR) from adjusted odds ratios, adjusted for the same variables. This study was registered with ClinicalTrials.gov, NCT02150980, and is ongoing. Findings: Between April 3, 2014, and May 10, 2019, we enrolled 31 255 patients with fractures, with a median age of 45 years (IQR 31–62), of whom 19 937 (63·8%) were men, and 14 524 (46·5%) had lower limb fractures, making them the most common fractures. Of 5256 patients with open fractures, 3778 (71·9%) were not admitted to hospital within 2 h. Of 25 999 patients with closed fractures, 7141 (27·5%) were delayed by more than 24 h. Of all regions, Latin America had the greatest proportions of patients with delays (173 [88·7%] of 195 patients with open fractures; 426 [44·7%] of 952 with closed fractures). Among patients delayed by more than 24 h, the most common reason for delays were interfacility referrals (3755 [47·7%] of 7875) and Third Delays (cumulatively interfacility referral and delay in emergency department: 3974 [50·5%]), while Second Delays (delays in reaching care) were the least common (423 [5·4%]). Compared with other methods of transportation (eg, walking, rickshaw), ambulances led to delay in transporting patients with open fractures to a treating hospital (adjusted RR 0·66, 99% CI 0·46–0·93). Compared with patients with closed lower limb fractures, patients with closed spine (adjusted RR 2·47, 99% CI 2·17–2·81) and pelvic (1·35, 1·10–1·66) fractures were most likely to have delays of more than 24 h before admission to hospital. Interpretation: In low-income and middle-income countries, timely hospital admission remains largely inaccessible, especially among patients with open fractures. Reducing hospital-based delays in receiving care, and, in particular, improving interfacility referral systems are the most substantial tools for reducing delays in admissions to hospital. Funding: National Health and Medical Research Council of Australia, Canadian Institutes of Health Research, McMaster Surgical Associates, and Hamilton Health Sciences