Coaxial recess integration of InGaAs/InP edge emitting laser diodes with waveguides on silicon substrates : a complete solution to laser integration on ICs

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2012.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (p. 279-289).In this thesis, the first demonstration of the full integration of 1.55[mu]m InGaAs/InP edge emitting platelet laser diodes with SiON/SiO2 dielectric waveguides on a silicon substrate is presented. Small footprint laser platelets (300[mu]m long by 150[mu mwide and 6.3[mu]m high), are integrated and bonded in recesses etched in SiO2 deposited on a Si substrate, and are coaxially coupled to the dielectric waveguides fabricated on the same wafer. Lasers assembled in 6.5[mu]m deep recesses are securely solder-bonded in place with a thin film Al/In bonding layer, which also brings the laser platelet back side n-contact to the wafer front side for measurements. The Al/In bonding layer composition and thickness are carefully optimized to provide highly reproducible vertical alignment to maximize the coupling of the laser output beam to the dielectric waveguide. Lasers are bonded into the recesses with this solder-bonding layer during a pressure assisted temperature cycle at 220°C. The low temperature nature of the bonding phase makes this integration technique CMOS compatible. The integrated lasers show lasing operation with threshold currents of Ith=17mA and Ith=19mA for pulsed and continuous wave drives respectively, at T=15°C. The output spectrum shows single mode lasing near 1550[mu]m, and a side mode suppression ratio of 25dB which is significantly higher than typical Fabry Perot cavity laser diodes. Furthermore, the integrated lasers have a characteristic temperature, T0, of 76K which is improved from 60K for non-integrated lasers. Also the integrated lasers consistently show lower threshold currents compared to their non-integrated counterparts. The coupling loss between the laser and dielectric waveguide is extracted to be as low as 1dB, a value that can be further reduced by improved horizontal alignment and better matching the widths of laser stripe and dielectric waveguide. Overall, this recess integration approach is CMOS compatible, is highly modular, compact and flexible, permits testing and selection of devices prior to integration, and allows integration of lasers emitting at different wavelengths on the same chip. It eliminates the need for wafer bonding III/V substrates to the host Si IC along with added complexity and cost it involves, and can be implemented using easily accessible technologies.by Shaya Famenini.Ph.D

Perspectives of people in Mali toward genetically-modified mosquitoes for malaria control

Background: Genetically-modified (GM) mosquitoes have been proposed as part of an integrated vector control strategy for malaria control. Public acceptance is essential prior to field trials, particularly since mosquitoes are a vector of human disease and genetically modified organisms (GMOs) face strong scepticism in developed and developing nations. Despite this, in sub-Saharan Africa, where the GM mosquito effort is primarily directed, very little data is available on perspectives to GMOs. Here, results are presented of a qualitative survey of public attitudes to GM mosquitoes for malaria control in rural and urban areas of Mali, West Africa between the months of October 2008 and June 2009. Methods: The sample consisted of 80 individuals - 30 living in rural communities, 30 living in urban suburbs of Bamako, and 20 Western-trained and traditional health professionals working in Bamako and Bandiagara. Questions were asked about the cause of malaria, heredity and selective breeding. This led to questions about genetic alterations, and acceptable conditions for a release of pest-resistant GM corn and malaria-refractory GM mosquitoes. Finally, participants were asked about the decision-making process in their community. Interviews were transcribed and responses were categorized according to general themes. Results: Most participants cited mosquitoes as one of several causes of malaria. The concept of the gene was not widely understood; however selective breeding was understood, allowing limited communication of the concept of genetic modification. Participants were open to a release of pest-resistant GM corn, often wanting to conduct a trial themselves. The concept of a trial was reapplied to GM mosquitoes, although less frequently. Participants wanted to see evidence that GM mosquitoes can reduce malaria prevalence without negative consequences for human health and the environment. For several participants, a mosquito control programme was preferred; however a transgenic release that satisfied certain requirements was usually acceptable. Conclusions: Although there were some dissenters, the majority of participants were pragmatic towards a release of GM mosquitoes. An array of social and cultural issues associated with malaria, mosquitoes and genetic engineering became apparent. If these can be successfully addressed, then social acceptance among the populations surveyed seems promising

The effects of diets enriched in omega-3 polyunsaturated fatty acids on systemic vaccinia virus infection

Omega-3 polyunsaturated fatty acids (PUFA, n-3 fatty acids), the key components of fish and flaxseed oils, are increasingly consumed by the public because of their potential health benefits and are available by prescription for hypertriglyceridemia. However, numerous studies have shown that these compounds are immunoregulatory and immunosuppressive and thus may increase susceptibility to infection. In this study, we tested the effects of the amount of fat and the types of fatty acid in the diet on infection by vaccinia virus, an acute infection that begins in the respiratory tract and spreads by viremia to internal organs. Male C57Bl6 mice (~5 week old) were fed for 3 weeks prior to infection and continuing during infection and recovery one of the following: 1) a normal low fat (13% kcal) diet, 2) a low fat diet containing n-3 PUFAs, 3) a high fat (41% kcal) diet rich in n-3 PUFAs, 4) a high fat n-6 PUFA diet, or 5) a high fat monounsaturated diet. We found no statistically significant differences in the susceptibility of mice to viral infection, morbidity, viral organ titers, recovery time, or mortality with these diets, indicating that, over this approximately 6-week time period, dietary fats did not substantially affect responses to poxviral infection

Adalimumab, etanercept and ustekinumab for treating plaque psoriasis in children and young people: systematic review and economic evaluation

Background: Psoriasis is a chronic inflammatory disease that predominantly affects the skin. Adalimumab (HUMIRA®, AbbVie, Maidenhead, UK), etanercept (Enbrel®, Pfizer, New York, NY, USA) and ustekinumab (STELARA®, Janssen Biotech, Inc., Titusville, NJ, USA) are the three biological treatments currently licensed for psoriasis in children. Objective: To determine the clinical effectiveness and cost-effectiveness of adalimumab, etanercept and ustekinumab within their respective licensed indications for the treatment of plaque psoriasis in children and young people. Data sources: Searches of the literature and regulatory sources, contact with European psoriasis registries, company submissions and clinical study reports from manufacturers, and previous National Institute for Health and Care Excellence (NICE) technology appraisal documentation. Review methods: Included studies were summarised and subjected to detailed critical appraisal. A network meta-analysis incorporating adult data was developed to connect the effectiveness data in children and young people and populate a de novo decision-analytic model. The model estimated the cost-effectiveness of adalimumab, etanercept and ustekinumab compared with each other and with either methotrexate or best supportive care (BSC), depending on the position of the intervention in the management pathway. Results: Of the 2386 non-duplicate records identified, nine studies (one randomised controlled trial for each drug plus six observational studies) were included in the review of clinical effectiveness and safety. Etanercept and ustekinumab resulted in significantly greater improvements in psoriasis symptoms than placebo at 12 weeks’ follow-up. The magnitude and persistence of the effects beyond 12 weeks is less certain. Adalimumab resulted in significantly greater improvements in psoriasis symptoms than methotrexate for some but not all measures at 16 weeks. Quality-of-life benefits were inconsistent across different measures. There was limited evidence of excess short-term adverse events; however, the possibility of rare events cannot be excluded. The majority of the incremental cost-effectiveness ratios for the use of biologics in children and young people exceeded NICE’s usual threshold for cost-effectiveness and were reduced significantly only when combined assumptions that align with those made in the management of psoriasis in adults were adopted. Limitations: The clinical evidence base for short- and long-term outcomes was limited in terms of total participant numbers, length of follow-up and the absence of young children. Conclusions: The paucity of clinical and economic evidence to inform the cost-effectiveness of biological treatments in children and young people imposed a number of strong assumptions and uncertainties. Health-related quality-of-life (HRQoL) gains associated with treatment and the number of hospitalisations in children and young people are areas of considerable uncertainty. The findings suggest that biological treatments may not be cost-effective for the management of psoriasis in children and young people at a willingness-to-pay threshold of £30,000 per quality-adjusted life-year, unless a number of strong assumptions about HRQoL and the costs of BSC are combined. Registry data on biological treatments would help determine safety, patterns of treatment switching, impact on comorbidities and long-term withdrawal rates. Further research is also needed into the resource use and costs associated with BSC. Adequately powered randomised controlled trials (including comparisons against placebo) could substantially reduce the uncertainty surrounding the effectiveness of biological treatments in biologic-experienced populations of children and young people, particularly in younger children. Such trials should establish the impact of biological therapies on HRQoL in this population, ideally by collecting direct estimates of EuroQol-5 Dimensions for Youth (EQ-5D-Y) utilities. Study registration: This study is registered as PROSPERO CRD42016039494. Funding: The National Institute for Health Research Health Technology Assessment programme

N-3 Polyunsaturated Fatty Acids and the Resolution of Neuroinflammation

In the past few decades, as a result of their anti-inflammatory properties, n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFAs), have gained greater importance in the regulation of inflammation, especially in the central nervous system (in this case known as neuroinflammation). If sustained, neuroinflammation is a common denominator of neurological disorders, including Alzheimer's disease and major depression, and of aging. Hence, limiting neuroinflammation is a real strategy for neuroinflammatory disease therapy and treatment. Recent data show that n-3 LC-PUFAs exert anti-inflammatory properties in part through the synthesis of specialized pro-resolving mediators (SPMs) such as resolvins, maresins and protectins. These SPMs are crucially involved in the resolution of inflammation. They could be good candidates to resolve brain inflammation and to contribute to neuroprotective functions and could lead to novel therapeutics for brain inflammatory diseases. This review presents an overview 1) of brain n-3 LC-PUFAs as precursors of SPMs with an emphasis on the effect of n-3 PUFAs on neuroinflammation, 2) of the formation and action of SPMs in the brain and their biological roles, and the possible regulation of their synthesis by environmental factors such as inflammation and nutrition and, in particular, PUFA consumption