Mechanical anisotropy in additive manufactured materials

Metal additive manufacturing (AM) is an innovative fabrication technique that enables processing of components with complex geometries and near-net shape dimensions providing design freedom and efficiency at unprecedented levels. The potential of AM has attracted significant interest from aerospace, automotive and medical device industries. While AM-processed materials can have superior mechanical properties compared to their conventionally processed counterparts, the layer-by-layer deposition of material often results in unique micro and mesostructural features that can lead to mechanical anisotropy. The focus of this thesis is to further our understanding of the impact of i) AM-processing techniques (laser-powder bed fusion (LPBF) and directed energy deposition (DED)) and ii) alloy systems (Al-Si alloys and a maraging steel) on structure formation and corresponding mechanical performance. A comprehensive investigation of LPBF processed Al-Si alloys indicates that the micro and mesostructural features significantly impact their tensile stress-strain and crack resistance curve (R-curve) behavior. As failure initiates along the melt pool boundaries, tensile samples that are tested along the build direction and fracture toughness samples that are tested with a crack propagating perpendicular to the build direction show reduced mechanical performance compared to their orthogonal counterparts. The differences between the directions, however, can be altered by changing processing parameters such as layer thickness, hatch spacing, and scan strategy. To understand the influence of AM technique on the anisotropy characteristics of the material, dual-wire arc DED was used to fabricate a compositionally graded Al-Si alloy. Results indicate that at low Si concentrations the tensile stress-strain behavior is impacted by the orientation of the samples with those tested along the build direction resulting in lower failure strain whereas the R-curves tested in different orientations were essentially identical. With increasing Si-concentration, however, the degree of anisotropy in both tensile and R-curve characteristics increase indicating an impact of chemical composition on mechanical performance. Compared to the Al-Si materials, results from the LPBF maraging steel show near-isotropic properties in both tensile stress-strain response and R-curve behavior due to the strong bonding characteristics between the individual layers. Although post-processing thermal treatments improve the mechanical performance of the material thereby enabling levels of damage tolerance that cannot be achieved with conventional processing methods, they additionally introduce anisotropy in R-curve behavior due to the formation of austenite along the melt pool boundaries

Changes in risk behaviours and prevalence of sexually transmitted infections following HIV preventive interventions among female sex workers in five districts in Karnataka state, south India

OBJECTIVES: To examine the impact of a large-scale HIV prevention programme for female sex workers (FSW) in Karnataka state, south India, on the prevalence of HIV/sexually transmitted infections (STI), condom use and programme coverage. METHODS: Baseline and follow-up integrated biological and behavioural surveys were conducted on random samples of FSW in five districts in Karnataka between 2004 and 2009. RESULTS: 4712 FSW participated in the study (baseline 2312; follow-up 2400), with follow-up surveys conducted 28-37 months after baseline. By follow-up, over 85% of FSW reported contact by a peer educator and having visited a project STI clinic. Compared with baseline, there were reductions in the prevalence of HIV (19.6% vs 16.4%, adjusted odds ratio (AOR) 0.81, 95% CI 0.67 to 0.99, p=0.04); high-titre syphilis (5.9% vs 3.4%, AOR 0.53, 95% CI 0.37 to 0.77, p=0.001); and chlamydia and/or gonorrhoea (8.9% vs 7.0%, AOR 0.72, 95% CI 0.54 to 0.94, p=0.02). Reported condom use at last sex increased significantly for repeat clients (66.1% vs 84.1%, AOR 1.98, 95% CI 1.58 to 2.48, p<0.001) and marginally for occasional clients (82.9% vs 88.0%, AOR 1.22, 95% CI 0.89 to 1.66, p=0.2), but remained stable for regular partners (32%). Compared with street and home-based FSW, brothel-based FSW were at highest risk of HIV and STI, despite high levels of reported condom use. CONCLUSIONS: This large-scale HIV prevention programme for FSW achieved reductions in HIV and STI prevalence, high rates of condom use with clients and high rates of programme coverage. Improved strategies to increase condom use with regular partners and reduce the vulnerability of brothel-based FSW to HIV are required

Changes in HIV and syphilis prevalence among female sex workers from three serial cross-sectional surveys in Karnataka state, South India.

OBJECTIVES: This paper examined trends over time in condom use, and the prevalences of HIV and syphilis, among female sex workers (FSWs) in South India. DESIGN: Data from three rounds of cross-sectional surveys were analysed, with HIV and high-titre syphilis prevalence as outcome variables. Multivariable analysis was applied to examine changes in prevalence over time. SETTING: Five districts in Karnataka state, India. PARTICIPANTS: 7015 FSWs were interviewed over three rounds of surveys (round 1=2277; round 2=2387 and round 3=2351). Women who reported selling sex in exchange for money or gifts in the past month, and aged between 18 and 49 years, were included. INTERVENTIONS: The surveys were conducted to monitor a targeted HIV prevention programme during 2004-2012. The main interventions included peer-led community outreach, services for the treatment and prevention of sexually transmitted infections, and empowering FSWs through community mobilisation. RESULTS: HIV prevalence declined significantly from rounds 1 to 3, from 19.6% to 10.8% (adjusted OR (AOR)=0.48, p<0.001); high-titre syphilis prevalence declined from 5.9% to 2.4% (AOR=0.50, p<0.001). Reductions were observed in most substrata of FSWs, although reductions among new sex workers, and those soliciting clients using mobile phones or from home, were not statistically significant. Condom use 'always' with occasional clients increased from 73% to 91% (AOR=1.9, p<0.001), with repeat clients from 52% to 86% (AOR=5.0, p<0.001) and with regular partners from 12% to 30% (AOR=4.2, p<0.001). Increased condom use was associated with exposure to the programme. However, condom use with regular partners remained low. CONCLUSIONS: The prevalences of HIV infection and high-titre syphilis among FSWs have steadily declined with increased condom use. Further reductions in prevalence will require intensification of prevention efforts for new FSWs and those soliciting clients using mobile phones or from home, as well as increasing condom use in the context of regular partnerships

Is Ghana’s pro-poor health insurance scheme really for the poor? Evidence from Northern Ghana

Protecting the poor and vulnerable against the cost of unforeseen ill health has become a global concern culminating in the 2005 World Health Assembly resolution urging member states to ensure financial protection to all citizens, especially children and women of reproductive age. Ghana provides financial protection to its citizens through the National Health Insurance Scheme (NHIS). Launched in 2004, its proponents claim that the NHIS is a pro-poor financial commitment that implements the World Health Assembly resolution. Using 2011 survey data collected in seven districts in northern Ghana from 5469 women aged 15 to 49 the paper explores the extent to which poor child-bearing age mothers are covered by the NHIS in Ghana’s poorest and most remote region. Factors associated with enrolment into the NHIS are estimated with logistic regression models employing covariates for household relative socio-economic status (SES), location of residence and maternal educational attainment, marital status, age, religion and financial autonomy. Results from the analysis showed that 33.9 percent of women in the lowest SES quintile compared to 58.3 percent for those in the highest quintile were insured. About 60 percent of respondents were registered. However, only 40 percent had valid insurance cards indicating that over 20 percent of the registered respondents did not have insurance cards. Thus, a fifth of the respondents were women who were registered but unprotected from the burden of health care payments. Results show that the relatively well educated, prosperous, married and Christian respondents were more likely to be insured than other women. Conversely, women living in remote households that were relatively poor or where traditional religion was practised had lower odds of insurance coverage. The results suggest that the NHIS is yet to achieve its goal of addressing the need of the poor for insurance against health related financial risks. To ultimately attain adequate equitable financial protection for its citizens, achieve universal health coverage in health care financing, and fully implement the World Health Assembly resolution, Ghana must reform enrolment policies in ways that guarantee pre-payment for the most poor and vulnerable households

A translational synthetic biology platform for rapid access to gram-scale quantities of novel drug-like molecules

Plants are an excellent source of drug leads. However availability is limited by access to source species, low abundance and recalcitrance to chemical synthesis. Although plant genomics is yielding a wealth of genes for natural product biosynthesis, the translation of this genetic information into small molecules for evaluation as drug leads represents a major bottleneck. For example, the yeast platform for artemisinic acid production is estimated to have taken >150 person years to develop. Here we demonstrate the power of plant transient transfection technology for rapid, scalable biosynthesis and isolation of triterpenes, one of the largest and most structurally diverse families of plant natural products. Using pathway engineering and improved agro-infiltration methodology we are able to generate gram-scale quantities of purified triterpene in just a few weeks. In contrast to heterologous expression in microbes, this system does not depend on re-engineering of the host. We next exploit agro-infection for quick and easy combinatorial biosynthesis without the need for generation of multi-gene constructs, so affording an easy entrée to suites of molecules, some new-to-nature, that are recalcitrant to chemical synthesis. We use this platform to purify a suite of bespoke triterpene analogs and demonstrate differences in anti-proliferative and anti-inflammatory activity in bioassays, providing proof of concept of this system for accessing and evaluating medicinally important bioactives. Together with new genome mining algorithms for plant pathway discovery and advances in plant synthetic biology, this advance provides new routes to synthesize and access previously inaccessible natural products and analogs and has the potential to reinvigorate drug discovery pipelines

Developing Effective Interuniversity Partnerships and Community-Based Research to Address Health Disparities

Health disparities are an enormous challenge to American society. Addressing these disparities is a priority for U.S. society and especially for institutions of higher learning, with their threefold mission of education, service, and research. Collaboration across multiple intellectual disciplines will be critical as universities address health disparities. In addition, universities must collaborate with communities, with state partners, and with each other. Development of these collaborations must be sensitive to the history and unique characteristics of each academic institution and population. The authors describe the challenges of all three types of collaboration, but primarily focus on collaboration between research-intensive universities and historically black colleges and universities