Design-for-Six-Sigma To Develop a Bioprocess Knowledge Management Framework

Owing to the high costs associated with biopharmaceutical development, considerable pressure has developed for the biopharmaceutical industry to increase productivity by becoming more lean and flexible. The ability to reuse knowledge was identified as one key advantage to streamline productivity, efficiently use resources, and ultimately perform better than the competition. A knowledge management (KM) strategy was assembled for bioprocess-related information using the technique of Design-for-Six-Sigma (DFSS). This strategy supported quality-by-design and process validation efforts for pipeline as well as licensed products. The DFSS technique was selected because it was both streamlined and efficient. These characteristics permitted development of a KM strategy with minimized team leader and team member resources. DFSS also placed a high emphasis on the voice of the customer, information considered crucial to the selection of solutions most appropriate for the current knowledge-based challenges of the organization. The KM strategy developed was comprised of nine workstreams, constructed from related solution buckets which in turn were assembled from the individual solution tasks that were identified. Each workstream's detailed design was evaluated against published and established best practices, as well as the KM strategy project charter and design inputs. Gaps and risks were identified and mitigated as necessary to improve the robustness of the proposed strategy. Aggregated resources (specifically expense/capital funds and staff) and timing were estimated to obtain vital management sponsorship for implementation. Where possible, existing governance and divisional/corporate information technology efforts were leveraged to minimize the additional bioprocess resources required for implementation. Finally, leading and lagging indicator metrics were selected to track the success of pilots and eventual implementation. LAY ABSTRACT: A knowledge management framework was assembled for bioprocess-related information using a streamlined and efficient technique that minimized team leader and member resources. The technique also highly emphasized input from the staff, who generated and used the knowledge, information considered crucial to selection of solutions most appropriate for the current knowledge-based challenges in the organization. The framework developed was comprised of nine workstreams, constructed from related solution buckets which were assembled from individual solution tasks that were identified. Each workstream's detailed design was evaluated against published and established best practices, as well as the project charter and design inputs. Gaps and risks were identified and mitigated to improve robustness of the proposed framework. Aggregated resources (specifically expense/capital funds and staff) and timing were estimated to obtain vital management sponsorship for implementation. Where possible, existing governance and information technology efforts were leveraged to minimize additional bioprocess resources required for implementation. Finally, metrics were selected to track the success of pilots and eventual implementation.     

Predicting aneurysm rupture probabilities through the application of a computed tomography angiography-derived binary logistic regression model

OBJECT:The goal of this study was to establish a biomathematical model to accurately predict the probability of aneurysm rupture. Biomathematical models incorporate various physical and dynamic phenomena that provide insight into why certain aneurysms grow or rupture. Prior studies have demonstrated that regression models may determine which parameters of an aneurysm contribute to rupture. In this study, the authors derived a modified binary logistic regression model and then validated it in a distinct cohort of patients to assess the model's stability. METHODS:Patients were examined with CT angiography. Three-dimensional reconstructions were generated and aneurysm height, width, and neck size were obtained in 2 orthogonal planes. Forward stepwise binary logistic regression was performed and then applied to a prospective cohort of 49 aneurysms in 37 patients (not included in the original derivation of the equation) to determine the log-odds of rupture for this aneurysm. RESULTS:A total of 279 aneurysms (156 ruptured and 123 unruptured) were observed in 217 patients. Four of 6 linear dimensions and the aspect ratio were significantly larger (each with p < 0.01) in ruptured aneurysms than unruptured aneurysms. Calculated volume and aneurysm location were correlated with rupture risk. Binary logistic regression applied to an independent prospective cohort demonstrated the model's stability, showing 83% sensitivity and 80% accuracy. CONCLUSIONS:This binary logistic regression model of aneurysm rupture identified the status of an aneurysm with good accuracy. The use of this technique and its validation suggests that biomorphometric data and their relationships may be valuable in determining the status of an aneurysm.     

Picroliv accelerates epithelialization and angiogenesis in rat wounds

Tissue repair and wound healing are complex processes that involve inflammation, granulation and tissue remodeling. Angiogenesis plays a central role in wound healing. Earlier, we have shown that picroliv, a natural product obtained from the roots of Picrorhiza kurrooa, up-regulates the expression of vascular endothelial growth factor in human umbilical vein endothelial cells and of insulin-like growth factor in rats during hypoxia. In the present study, we have investigated the effect of picroliv in an ex vivo rat aorta ring model of angiogenesis. Picroliv enhanced the sprouting and migration of endothelial cells. We also investigated punch wound healing on days 4 and 7 after wounding by histology, morphometry and collagenization. The data showed improved re-epithelialization, neovascularization and migration of various cells such as endothelial, dermal myofibroblasts and fibroblasts into the wound bed after picroliv treatment. Immunohistochemical localization showed increased VEGF and alpha smooth muscle actin staining consistent with an increased number of microvessels in granulation tissue. These findings suggest that picroliv could be developed as a therapeutic angiogenic agent for the restoration of the blood supply in diseases involving inadequate blood supply such as limb ischemia, ischemic myocardium and wound healing.     

Evaluation of gelatin/resorcinol/aldehyde as a hemostatic agent and tissue adhesive: an experimental study in rat

Use of gelatin/resorcinol/formaldehyde glue as a tissue adhesive and hemostatic agent was evaluated experimentally after modification of the aldehyde component. Gelatin/ resorcinol/aldehyde (GRA) glue was prepared by mixing gelatin and resorcinol and cross-linking with a blend of formaldehyde/glutaraldehyde. After wedge resection of the liver of 28 albino rats, bleeding was controlled, and the cut surfaces were joined with GRA. Liver biopsy was done at 7, 14, 21, and 28-day intervals. Hemostasis was excellent in 71.4%, satisfactory in 25.0%, and poor in 3.6%. Mean time for tissue adhesion was 2.6 minutes. No necrosis or bile leakage was seen. Visibility of site of repair decreased from 50.0% on day 7 to 14.3% on day 28. Residual glue was seen microscopically on day 28 in 43% cases. GRA is safe and good hemostatic, tissue adhesive, and sealant in rat liver.     

Green tea polyphenols and its constituent epigallocatechin gallate inhibits proliferation of human breast cancer cells in vitro and in vivo

Tea [Camellia sinensis (Theaceae)] intake is second only to water in terms of worldwide popularity as a beverage. The Green tea polyphenols have been shown to have a protective effect in prostate cancer in various pre-clinical animal models and has been reported to be effective in several other cancer types as well. An inverse association between the risk of breast cancer and the intake of green tea has also been reported in Asian Americans. Several epidemiological studies have shown that breast cancer progression is delayed in the Asian population that consumes green tea on regular basis. In this study, we report the effectiveness of green tea polyphenols (GTP) and its constituent Epigallocatechin Gallate (EGCG) in tumor regression using both in-vitro cell culture models and in vivo athymic nude mice models of breast cancer. The anti-proliferative effect of GTP and EGCG on the growth of human breast cancer MDA-MB-231 cell was studied using a tetrazolium dye-based (MTT) assay. Both GTP and EGCG treatment had the ability to arrest the cell cycle at G1 phase as assessed by flow cytometry. The expression of Cyclin D, Cyclin E, CDK 4, CDK 1 and PCNA were down regulated over the time in GTP and EGCG treated experimental group, compared to the untreated control group as evaluated by western blot analysis for cell cycle proteins, which corroborated the G1 block. Nude mice inoculated with human breast cancer MDA-MB-231 cells and treated with GTP and EGCG were effective in delaying the tumor incidence as well as reducing the tumor burden when compared to the water fed and similarly handled control. GTP and EGCG treatment were also found to induce apoptosis and inhibit the proliferation when the tumor tissue sections were examined by immunohistochemistry. Our results suggest that GTP and EGCG treatment inhibits proliferation and induce apoptosis of MDA-MB-231 cells in-vitro and in-vivo. All together, these data sustain our contention that GTP and EGCG have anti-tumor properties.     

Spontaneous transdiaphragmatic intercostal hernia: a rare clinical entity

The herniation of abdominal contents through a diaphragmatic and chest wall rent has been uncommonly reported in literature. Also known as a transdiaphragmatic intercostal hernia (TDIH) or intercostal pleuroperitoneal hernia, it occurs when the disruption of diaphragmatic or intercostal muscles leads to an acquired herniation of abdominal contents. It is usually seen to occur following a traumatic incident. We report the case of an elderly male who presented with a reducible lump in the left chest and breathlessness on exertion, in the absence of any trivial or occult trauma, and how this was managed adequately via surgery alone.     

Profile of Clients Tested HIV Positive in a Voluntary Counseling and Testing Center of a District Hospital, Udupi, South Kannada

Background:The growing menace created by the HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) has alarmed not only the public health officials but also the general community. The Voluntary Counseling and Testing Centre (VCTC) services have begun as a cost-effective intervention in reversing this epidemic.Objectives:1. To study the sociodemographic characteristics of HIV-positive clients and their risk behaviors. 2. To elucidate the reasons for their visit to the VCTC and know the problems anticipated by the clients after revealing their HIV-positive status.Results:Study included 249 individuals, of whom 64.7% were males, 88.7% (age, 15–49 years), married (72.7% males and 84.0% females) and literate (females 71.5% and males 85.7%). A high percentage of nonresponse regarding the pattern of risk behavior was noted among the subjects (males: 42.8% and females: 90.9%). Of the individuals who responded, 91 males (98.9%) and 6 females (75.0%) had multiple heterosexual sex partners, while 1 male had homosexual partner. The figures in females show that two (25%) of them had a history of blood transfusion. The reason for visiting the VCTC were cited as some form of illness (33.3%), confirmation of test results (32.9%), family members diagnosed as HIV positive (12.9%) and 11.6% were referred from Directly Observed Treatment Scheme (DOTS) center. More than three quarter of the sample population anticipated discrimination at the time of medical treatment.Conclusion:People have begun using VCTC services, which reflects a change in their attitude toward HIV. The study provides us a clue to formulate an effective approach to educate people as well as the health personnel who are thought of as one of the important sources of discrimination.     

Malaria Free India – Possibility or Enigma?

Malaria, despite being treatable as well as preventable, is still quite prevalent in our country and is responsible for a large number of deaths. Though Govt. of India (GOI) has launched anti-malaria program since 1953 but is yet to achieve a zero malaria status. In SE Asia, two small countries, Maldives and Sri Lanka, have been declared Malaria free by WHO. Hence, we need to think why we cannot achieve this status? For this we need to study how these two countries were successful and what are our limitations/pitfalls. The medical profession has a great role to play. Not only we have to advise GOI to formulate the correct policy but also we need to plug the rampant pitfalls in our practice. Implementation of WHO’s 3 T (Test, treat and track) policy can be a table turner.