Biological Engineering: Advances and Methods

The last few decades have seen a tremendous growth in the field of bioengineering. As the need for further treatment and innovation for tissue repair, partial to full organ replication, and gene therapy continues to increase, the field of bioengineering will be tasked with curing and preventing disease and traumatic injuries. The two primary fields currently being focused on in the lab are the way cells interact and communicate to build tissues, and the nature and materials utilized in scaffolding to allow differentiation and migration when cells are seeded. Within those two fields are subsets of different methods, materials that vary greatly. Some stem cells offer certain benefits, yet lack viability due to a host of obstacles, such as ethical questions about their procurement, to their technical obstacles, such as materials utilized for best profusion in a scaffold. It appears that proper and adequate funding for research into finding solutions will be pivotal in having the next medical breakthrough in science. It may very well be referred as one of the greatest advancements in modern history and forever change the face of science should this technology become successful and accessible. Indeed, recent successes in patients would be a strong indicator that this technology and innovation is not too distant in the future

The Penitentiary and Perfectibility in Tocqueville

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68614/2/10.1177_106591298503800103.pd

Is the Association of Airborne Particles with Daily Deaths Confounded by Gaseous Air Pollutants? An Approach to Control by Matching

Although particulate air pollution has been associated with increased numbers of daily deaths in dozens of cities around the world, issues still remain about the association. Some have questioned the complex modeling used to control for season in Poisson regression or the role of gaseous air pollutants as potential confounders of the association. I examined the association between deaths and particulate matter with an aerodynamic diameter less than or equal to 10 microm (PM10) using a case-crossover design. In this approach, the pollution on the day of each death is contrasted with the pollution level on control days when the subject did not die. Season and gaseous air pollutants were controlled by matching. Control days were chosen within the same month of the same year to control for season, and matched on either sulfur dioxide (SO2; within 1 ppb), nitrogen dioxide (within 1 ppb), maximum ozone (within 2 ppb), or carbon monoxide (within 0.03 ppm). The analysis was conducted in 14 U.S. cities that have daily PM10 monitoring. After matching, there were about 400,000 deaths in each analysis. Results were combined across cities using a maximum likelihood method. PM10 was a significant predictor of mortality when controlling for gaseous air pollutants, with effect sizes ranging from a 0.45% increase per 10 microg/m3 increment of PM10 [95% confidence interval (CI), 0.12-0.79%] when matched on maximum hourly ozone levels, to a 0.81% increase per 10 microg/m3 increment of PM10 (95% CI, 0.47-1.16%) when matched on 24-hr average SO2

Understanding Escherichia coli Urinary Tract Infection: A Niche Perspective

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, costing greater than $2 billion in healthcare costs and lost wages yearly in America alone. The lifetime risk for a woman exceeds 50% with 25-40% of these suffering recurrent infections. Two of the most important risk factors for recurrent UTI are prior UTIs and sexual intercourse. Over 80% of UTIs are caused by uropathogenic Escherichia coli (UPEC), which binds and invades superficial facet cells lining the bladder surface. UPEC expresses extracellular fibers called type 1 pili with a terminal mannose-binding adhesin, FimH, which interacts with mannosylated uroplakin residues on the urothelium. UPEC replicates in the cytoplasm of bladder cells into biofilm-like intracellular bacterial communities (IBCs) in a protected niche. In C3H/HeN mice, a robust, systemic, immune response at 24 hours precedes the development of persistent bacteriuria and chronic cystitis, which lasts indefinitely. A less robust immune response results in resolution of the infection. I determined the population dynamics during UPEC infection with a set of 40 variants of a clinical isolate, UTI89, each with a unique genetic sequence detectable by multiplex PCR. I identified a significant population bottleneck during the first 24 hours coinciding with the inflammatory response. Furthermore, I tested a panel of FimH alleles under positive selection and found several that impacted the ability of UPEC strains to form IBCs and promote chronic cystitis. These pathoadaptive alleles govern the ability of FimH to bind mannose by dynamically interconverting between a compact, low-affinity conformation and an elongated, high-affinity state. This dynamic equilibrium is crucial for virulence as alleles locked in either conformation are attenuated. I also developed a model of frequent inoculation of UPEC into the urinary tract to investigate the clinical link between frequent sexual intercourse and UTI risk. By inoculating mice twice during acute infection, I found a dramatic increase in the proportion of mice that experienced chronic cystitis. Taken together, this thesis defines bacterial and behavioral factors that increase the risk for chronic and recurrent UTI, providing rationale for the development of novel therapeutics targeting bacterial invasion to limit infection by excluding UPEC from intracellular niches

A Regulatory Analysis of EPA's Proposed Rule to Reduce Mercury Emissions from Utility Boilers

EPA's proposed rule for mercury reductions from coal-fired utility boilers is unlikely to provide significant health benefits, both because mercury exposure at current levels is unlikely to be causing harm, and because even in a best case scenario the mercury rule could reduce mercury in fish by no more than a few percent. The claim that reducing mercury in fish will reduce neurological harm to fetuses of exposed pregnant women is based on the assumptions that the results of an epidemiologic study of mothers and children in the Faroe Islands represents a genuine cause-effect relationship between low-level mercury exposure and children's neurological health, and that Faroes-like effects would occur in Americans even at mercury exposures as low as 1/15th the minimum level associated with health effects in the Faroes study. But even accepting these assumptions at face value, the reported health effects are subtle and at current American mercury exposure levels have no implications for general neurological or cognitive health. For example, based on the Faroes results, a complete elimination of U.S. utility mercury emissions could, in a best-case scenario, move children who are at, say, the 10th percentile on neurological and cognitive test scores to between the 10.3 and 10.6 percentiles. Even this small improvement is unrealistically optimistic, because it also assumes a one-to-one correspondence between mercury emission reductions and mercury levels in freshwater fish, and that people with high mercury exposures receive all of their mercury from non-commercial, freshwater fish. Furthermore, a similar study of children in the Seychelles reported no harm from mercury exposures several times higher than even relatively highly exposed Americans. The Seychelles study may be more relevant to Americans, because people in the Seychelles are exposed to mercury through eating ocean fish, while people in the Faroe Islands are exposed through eating whale blubber. EPA's mercury rule is thus likely to provide few or no health benefits. On the other hand, EPA estimates even modest utility mercury reductions will cost about $1.4 billion per year. These costs will in part be passed through to consumers, reducing the resources available for other health- and welfare-enhancing expenditures. If EPA still wishes to go forward with utility regulations, rather than regulate mercury directly, EPA should scrap both its mercury rule and its companion Interstate Air Quality Rule, which would regulate utility nitrogen oxides and sulfur dioxide (SO2), and instead require reductions only in SO2 emissions. SO2 reductions will reduce mercury levels in fish by reducing sulfate levels in lakes and streams, which reduces methylmercury formation, the form of mercury that gets into fish and to which people are exposed. Furthermore, the SO2 reductions will reduce mercury in freshwater fish regardless of where the mercury in fish is coming from and will cost less than mercury reductions. SO2 reductions will also reduce sulfate particulate matter and regional haze, and the measures necessary to reduce SO2 emissions will also modestly reduce mercury emissions. While the costs of additional SO2 reductions might still outweigh their benefits, the cost-benefit picture for utility SO2 reductions is far superior to even the most generous best-case benefit estimates for EPA's proposed utility mercury rule.