Understanding the Role of Phosphoinositide 3-Kinase and its Function as a Driving Force behind the ER Stress Response in Fibrostenotic Crohn’s Disease-affected Ileal Smooth Muscle Cells

Crohn’s disease (CD) affects about 780,000 people in the United States alone, and it is estimated that 6-15 per 100,000 persons will receive a diagnosis of this disease each year. There currently is no cure for Crohn’s disease, and available medical therapies simply serve to alleviate the inflammation. This does not help treat fibrostenosis that Crohn’s disease patients may develop, which can only be treated surgically. Finding alternatives to treat CD requires an understanding of mechanisms at the biochemical level. In this thesis, we attempted to gain a better understanding of certain pathways found to be active in Crohn’s disease-affected ileal smooth muscle cells. We found an upregulation of the ER stress pathway via expression of its surrogate, the GRP78 protein. We also showed evidence that the phosphoinositide 3-kinase (PI3K) pathway, a key proliferative pathway, is linked to ER stress in these cells, and is an upstream driving force of the ER stress response. Further research on the link between the PI3K and ER stress pathways needs to be conducted, and can potentially serve as a target for therapeutics to help reduce proliferation in fibrostenotic Crohn’s disease-affected ileal smooth muscle cells

Countering Drug Resistance in the Developing World: An Assessment of Incentives across the Value Chain and Recommendations for Policy Interventions

The emergence and spread of drug resistance is draining available resources and threatening our ability to treat infectious diseases in developing countries. HIV/AIDS, tuberculosis, malaria, diarrhea, and respiratory tract infections continue to be the leading causes of death in many developing countries, many of which have already been exacerbated by resistance. Countering drug resistance often involves complex tradeoffs between activities such as the development of new products; ensuring treatment heterogeneity; and guaranteeing quality and ensuring systemic availability, affordability, compliance, adherence and rational use of drugs and diagnostics. A careful understanding of all the players involved in the resistance problem and their incentives to engage in activities that counter drug resistance is crucial for policymakers and resource managers in a range of institutions and agencies. This paper presents results gathered through quasi-structured interviews to understand these incentives and develop recommendations to better align them with resistance-countering activities.drug resistance; developing countries; HIV/AIDS; supply chains; drugs; diagnostics; recommendations; policy

National Drug Stockout Risks in Africa: Analysis of the Global Fund Disbursement Process for Procurement from 2002 to 2013​

Despite substantial financial aid from international donors for procurement of health products, stockouts of life-saving drugs related to prevalent infectious diseases are still widespread in Africa. Addressing the lack of research on why these stockouts occur, we study the relationship between The Global Fund to Fight AIDS, Tuberculosis and Malaria and its grant recipients. Specifically, we leverage extensive historical fund disbursement and drug procurement data to build a discrete-event simulation model predicting the joint impact of procurement and grant disbursement processes on national drug availability for the Global Fund’s recipient countries in Africa. This model is validated against cumulative stockout levels inferred from historical grant implementation lengths, and used to evaluate potential high-level modifications of disbursement or procurement processes. Results show the existence of substantial intrinsic stockout risks in many countries, due to the unpredictability of fund disbursements and the frequency of grant performance monitoring performed by the Global Fund. Interventions increasing fund disbursement levels to protect against disbursement timing uncertainty are predicted to be more effective than others that include regional buffer stocks and bridge financing.http://deepblue.lib.umich.edu/bitstream/2027.42/107445/1/1241_Yadav.pd

Optimal Supply Chain Structure for Distributing Essential Drugs in Low Income Countries: Results from a Randomized Experiment

Despite increased investments in health commodity procurement, the availability of essential medicines at health facilities remains very low in many low and middle income countries. The lack of a well-functioning supply chain for essential medicines is often the cause of this poor availability. Using a randomized experiment conducted in over 400 health facilities and 24 districts in Zambia, this study helps understand the optimal supply chain structure for essential medicines distribution in the public sector in low income countries. It focuses on the availability of 15 essential medicines at the health facility level and compares between a cross-dock based two-tier distribution network and a three-tier network. The study shows that a two-tier “cross- dock” like system outperforms a traditional three-tier drug distribution system due to better information flow and better management accountability even though stock is positioned closer to the health facilities in the three-tier system. Results from the study advance existing knowledge in the area of public sector distribution system design in general and drug distribution systems in developing countries in particular.http://deepblue.lib.umich.edu/bitstream/2027.42/110800/1/1269_Yadav.pd

Improved Dynamic Parallel K-Means Algorithm using Dunn?s Index Method

K-Means is popular and widely used clustering technique in present scenario. Many research has been done in same area for the improvement of K-Means clustering algorithm, but further investigation is always required to reveal the answers of the important questions such as ?is it possible to find optimal number of clusters dynamically while ignoring the empty clusters? or ?does the parallel execution of any clustering algorithm really improves it performance in terms of speedup?. This research presents an improved K-Means algorithm which is capable to calculate the number of clusters dynamically using Dunn?s index approach and further executes the algorithm in parallel using the capabilities of Microsoft?s Task Parallel Libraries. The original K-Means and Improved parallel modified K-Means algorithm performed for the two dimensional raw data consisting different numbers of records. From the results it is clear that the Improved K-Means is better in all the scenarios either increase the numbers of clusters or change the number of records in raw data. For the same number of input clusters and different data sets in original K-Means and Improved K-Means, the performance of Modified parallel K-Means is 20 to 50 percent better than the original K-Means in terms of Execution time and Speedup

Five factors that drive successful large-scale vaccine distribution

What factors make for a successful vaccine rollout? Prashant Yadav (Center for Global Development/INSEAD) explains five of the key operational levers and choices that governments need to make

Supply Chains and Global Health: An Imperative for Bringing Operations Management Scholarship into Action

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97270/1/poms1315.pd

Characterization of Zinc oxide & Aluminum Ferrite and Simulation studies of M-H plots of Cobalt/Cobaltoxide

Zinc oxide and Aluminum Ferrite were prepared Chemical route. The samples were characterized by XRD and VSM. Simulation of M-H plots of Co/CoO thin films were performed. Effect of parameters was observed on saturation magnetization.Comment: Working paper (11 pages, 8 figures

Thyroid abnormality in abnormal uterine bleeding: an observational study from Medical College in Western UP, India

Background: Abnormal Uterine Bleeding (AUB) is one of the commonest gynecological complain in reproductive age group. Menstrual abnormalities are commonly seen when there is any alteration in thyroid function. Objective of present study was to investigate the prevalence of AUB and to determine the menstrual pattern in cases with thyroid dysfunction.Methods: The present cross sectional observational study was conducted Teerthankar Mahaveer Medical College and Research Center Moradabad. Total 400 cases presenting with AUB were included in the study. Routine blood test, ultrasonography and thyroid function tests were done in these cases.Results: Among all the cases presenting with menstrual abnormalities 26% had hypothyroidism and 9% have hyperthyroidism and rest had euthyroid status. Menorrhagia (45.2%) and polymenorrhoea (37.5%) were commonest menstrual abnormality seen in cases with hypothyroidism. Most cases with hyperthyroidism presented with hypomenorrhoea (27.8%).Conclusions: Thyroid function abnormality is common in cases presenting with AUB and it gets relieved in correcting hormonal imbalance