Manufacturing single use systems with quality in mind: How to assure performance, robustness, and sterility of single use systems

Quality control during the manufacturing of single use systems is critical. With traditional stainless-steel systems, the end user has significant control over the design, construction, qualification, validation, and maintenance of the system. When implementing a single-use system, the supplier of the single use product takes responsibility for many of these functions from the user. It is therefore important that the single use supplier has established and uses a robust quality control system. This presentation will highlight the quality systems, processes, facilities, and personnel required to assure the performance, robustness, and sterility of single use systems. The following topics will be covered: Single-use assembly validation Qualification of components Sterilization qualification Manufacturing processes Quality control Release testing Certification Risk mitigation practices Process particulate control Operator training Leachables & Extractables Patient safety evaluation, study design Support by the supplie

Mast cell subsets and their functional modulation by the Acanthocheilonema viteae product ES-62

ES-62, an immunomodulator secreted by filarial nematodes, exhibits therapeutic potential in mouse models of allergic inflammation, at least in part by inducing the desensitisation of Fc휀RI-mediated mast cell responses. However, in addition to their pathogenic roles in allergic and autoimmune diseases, mast cells are important in fighting infection, wound healing, and resolving inflammation, reflecting that mast cells exhibit a phenotypic and functional plasticity. We have therefore characterised the differential functional responses to antigen (via Fc휀RI) and LPS and their modulation by ES-62 of the mature peritoneal-derived mast cells (PDMC; serosal) and those of the connective tissue-like mast cells (CTMC) and themucosal-likemast cells derived from bone marrow progenitors (BMMC) as a first step to produce disease tissue-targeted therapeutics based on ES-62 action. All three mast cell populations were rendered hyporesponsive by ES-62 and whilst the mechanisms underlying such desensitisation have not been fully delineated, they reflect a downregulation of calcium and PKC훼 signalling. ES-62 also downregulatedMyD88 and PKC훿 in mucosal-type BMMC but not PDMC, the additional signals targeted in mucosal-type BMMC likely reflecting that these cells respond to antigen and LPS by degranulation and cytokine secretion whereas PDMC predominantly respond in a degranulationbased manner

Adherence to Canada's Food Guide Recommendations during Pregnancy:Nutritional Epidemiology and Public Health

Background: In Canada, pregnant women are typically referred to Canada's Food Guide (CFG), a set of national dietary recommendations designed to promote adequate nutrient intake. Pregnant women are also advised to gain weight within the Institute of Medicine guidelines, which differ by prepregnancy body mass index (BMI). However, CFG recommendations do not account for prepregnancy BMI and provide no guidance on "less healthy" (LH) foods. Objective: The aim of this study was to score women's diets according to adherence to CFG recommendations and consumption of LH foods and to examine differences between these diet scores by prepregnancy BMI. Methods: Participants enrolled in the APrON (Alberta Pregnancy Outcomes and Nutrition) prospective cohort study completed a 24-h recall in their second trimester (n = 1630). A score was created on the basis of each daily dietary CFG recommendation met, ranging from 0 to 9. The distribution of consumption (grams per day) of 8 LH food groups was given a score of 0 (none) or 1, 2, or 3 (representing the lowest, middle, or highest tertiles, respectively) and summed giving a total LH score of 0-24. Results: There were few differences in CFG recommendations met by prepregnancy BMI status, although fewer women who were overweight or obese prepregnancy met the specific recommendation to consume 7-8 servings of fruit or vegetables/d than did those who were under- or normal weight (47% and 41% compared with 50% and 54%, respectively). Although differences were small, women who were obese prepregnancy had lower CFG scores (β = -0.28; 95% CI:-0.53, -0.02) and higher LH scores (β = 0.45; 95% CI: 0.04, 0.86) than did those who were normal weight. Conclusion: The study results suggest that more attention may need to be paid to individualized counseling on dietary recommendations that take account of prepregnancy BMI

Algebraic tools for dealing with the atomic shell model. I. Wavefunctions and integrals for hydrogen--like ions

Today, the 'hydrogen atom model' is known to play its role not only in teaching the basic elements of quantum mechanics but also for building up effective theories in atomic and molecular physics, quantum optics, plasma physics, or even in the design of semiconductor devices. Therefore, the analytical as well as numerical solutions of the hydrogen--like ions are frequently required both, for analyzing experimental data and for carrying out quite advanced theoretical studies. In order to support a fast and consistent access to these (Coulomb--field) solutions, here we present the Dirac program which has been developed originally for studying the properties and dynamical behaviour of the (hydrogen--like) ions. In the present version, a set of Maple procedures is provided for the Coulomb wave and Green's functions by applying the (wave) equations from both, the nonrelativistic and relativistic theory. Apart from the interactive access to these functions, moreover, a number of radial integrals are also implemented in the Dirac program which may help the user to construct transition amplitudes and cross sections as they occur frequently in the theory of ion--atom and ion--photon collisions.Comment: 23 pages, 1 figur

Dendritic cells provide a therapeutic target for synthetic small molecule analogues of the parasitic worm product, ES-62

ES-62, a glycoprotein secreted by the parasitic filarial nematode Acanthocheilonema viteae, subverts host immune responses towards anti-inflammatory phenotypes by virtue of covalently attached phosphorylcholine (PC). The PC dictates that ES-62 exhibits protection in murine models of inflammatory disease and hence a library of drug-like PC-based small molecule analogues (SMAs) was synthesised. Four sulfone-containing SMAs termed 11a, 11e, 11i and 12b were found to reduce mouse bone marrow-derived dendritic cell (DC) pathogen-associated molecular pattern (PAMP)-induced pro-inflammatory cytokine production, inhibit NF-κB p65 activation, and suppress LPS-induced up-regulation of CD40 and CD86. Active SMAs also resulted in a DC phenotype that exhibited reduced capacity to prime antigen (Ag)-specific IFN-γ production during co-culture with naïve transgenic TCR DO.11.10 T cells in vitro and reduced their ability, following adoptive transfer, to prime the expansion of Ag-specific T lymphocytes, specifically TH17 cells, in vivo. Consistent with this, mice receiving DCs treated with SMAs exhibited significantly reduced severity of collagen-induced arthritis and this was accompanied by a significant reduction in IL-17+ cells in the draining lymph nodes. Collectively, these studies indicate that drug-like compounds that target DCs can be designed from parasitic worm products and demonstrate the potential for ES-62 SMA-based DC therapy in inflammatory disease

Energy Content of Colliding Plane Waves using Approximate Noether Symmetries

This paper is devoted to study the energy content of colliding plane waves using approximate Noether symmetries. For this purpose, we use approximate Lie symmetry method of Lagrangian for differential equations. We formulate the first-order perturbed Lagrangian for colliding plane electromagnetic and gravitational waves. It is shown that in both cases, there does not existComment: 18 pages, accepted for publication in Brazilian J Physic

Kinetochore genes are coordinately up-regulated in human tumors as part of a FoxM1-related cell division program

The key player in directing proper chromosome segregation is the macromolecular kinetochore complex, which mediates DNA–microtubule interactions. Previous studies testing individual kinetochore genes documented examples of their overexpression in tumors relative to normal tissue, leading to proposals that up-regulation of specific kinetochore genes may promote tumor progression. However, kinetochore components do not function in isolation, and previous studies did not comprehensively compare the expression behavior of kinetochore components. Here we analyze the expression behavior of the full range of human kinetochore components in diverse published expression compendia, including normal tissues and tumor samples. Our results demonstrate that kinetochore genes are rarely overexpressed individually. Instead, we find that core kinetochore genes are coordinately regulated with other cell division genes under virtually all conditions. This expression pattern is strongly correlated with the expression of the forkhead transcription factor FoxM1, which binds to the majority of cell division promoters. These observations suggest that kinetochore gene up-regulation in cancer reflects a general activation of the cell division program and that altered expression of individual kinetochore genes is unlikely to play a causal role in tumorigenesis.Leukemia & Lymphoma Society of America (Scholar Award)National Institute of General Medical Sciences (U.S.) (Grant GM088313)American Cancer Society (Research Scholar Grant 121776)National Science Foundation (U.S.). Graduate Research Fellowshi

Short-Term Rationing of Combination Antiretroviral Therapy: Impact on Morbidity, Mortality, and Loss to Follow-Up in a Large HIV Treatment Program in Western Kenya

Background. There was a 6-month shortage of antiretrovirals (cART) in Kenya. Methods. We assessed morbidity, mortality, and loss to follow-up (LTFU) in this retrospective analysis of adults who were enrolled during the six-month period with restricted cART (cap) or the six months prior (pre-cap) and eligible for cART at enrollment by the pre-cap standard. Cox models were used to adjust for potential confounders. Results. 9009 adults were eligible for analysis: 4,714 pre-cap and 4,295 during the cap. Median number of days from enrollment to cART initiation was 42 pre-cap and 56 for the cap (P < 0.001). After adjustment, individuals in the cap were at higher risk of mortality (HR = 1.21; 95% CI : 1.06–1.39) and LTFU (HR = 1.12; 95% CI : 1.04–1.22). There was no difference between the groups in their risk of developing a new AIDS-defining illness (HR = 0.92 95% CI 0.82–1.03). Conclusions. Rationing of cART, even for a relatively short period of six months, led to clinically adverse outcomes

Oil disturbance reduces infaunal family richness but does not affect phylogenetic diversity

Infaunal organisms are susceptible to disturbances such as hypoxia and sediment contamination; changes in infaunal community structure are therefore often used as indicators of anthropogenic disturbance. Susceptibility to disturbance varies across taxa, either due to physiological factors or to behaviors or functional roles that increase exposure. Both sources of variability are likely to be heritable and shared among related taxa. Thus, we would expect oil disturbance to disproportionately affect related taxa and therefore decrease phylogenetic diversity (PD). We test this hypothesis for a shallow water marine infaunal community using a simulation approach that iteratively removes clades with shared vulnerability to oil exposure. Infauna were sampled at two sites in the Chandeleur Islands, LA, that reflect different exposures to crude oil after the Deepwater Horizon event. Seagrass and adjacent bare sediment habitats were sampled in 2015, 5 years after initial oil exposure, and again in 2016 after an acute re-oiling event. We found that strong correlation between PD and family richness masked any detectable PD patterns with oil exposure. For our full community tree, sensitivity analysis indicated that the removal of larger clades did not disproportionately reduce PD, against our prediction. For this pair of sites, PD did not provide a better metric for assessing the impacts of oil exposure than family richness alone. It is possible, however, that finer-scale taxonomic resolution of infaunal communities may better decouple PD from taxonomic richness. More work is needed to fully evaluate the impacts of disturbance on PD