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In the summer of 1883 Belgian travel writer Jules Leclercq spent ten days on horseback in Yellowstone, the world's first national park, exploring myriad natural wonders: astonishing geysers, majestic waterfalls, the vast lake, and the breathtaking canyon. He also recorded the considerable human activity, including the rampant vandalism. Leclercq's account of his travels is itself a small marvel blending natural history, firsthand impressions, scientific lore, and anecdote. Along with his observations on the park's long-rumored fountains of boiling water and mountains of glass, Leclercq describes camping near geysers, washing clothes in a bubbling hot spring, and meeting such diverse characters as local guides and tourists from the United States and Europe. Notables including former president Ulysses S. Grant and then-president Chester A. Arthur were also in the park that summer to inaugurate the newly completed leg of the Northern Pacific Railroad. A sensation in Europe, the book was never published in English. This deft translation at long last makes available to English-speaking readers a masterpiece of western American travel writing that is a fascinating historical document in its own right.

The macrocyclic core of the antibiotic erythromycin, 6-deoxyerythronolide B (6dEB), is a complex natural product synthesized by the soil bacterium Saccharopolyspora erythraea through the action of a multifunctional polyketide synthase (PKS). The engineering potential of modular PKSs is hampered by the limited capabilities for molecular biological manipulation of organisms (principally actinomycetes) in which complex polyketides have thus far been produced. To address this problem, a derivative of Escherichia coli has been genetically engineered. The resulting cellular catalyst converts exogenous propionate into 6dEB with a specific productivity that compares well with a high-producing mutant of S. erythraea that has been incrementally enhanced over decades for the industrial production of erythromycin.

The value of programme logic models as a tool for planning, evaluation, and communication is well recognised. However, the value of its development process is less discussed. In this paper, we describe how we used a combination of literature review and organisational stakeholder consultations to develop a logic model for a telehealth programme for children in rural and remote Australia. Our aim was to use this process to further embed the programme within its implementing organisation, and by so doing to promote its sustainability and scale-up; a major challenge of telehealth programmes, especially those involving reorganisation of processes. Our efforts to describe the components of this complex intervention on the one-page logic model allowed for debates and discussions within the implementing organisation which then facilitated an improved cross-organisational understanding of the telehealth programme; a real time face-to-face (video-link) service which requires the reorganisation of existing service delivery platforms. The process helped to embed the telehealth programme within existing services. We conclude that stakeholder engagement in developing logic models can transform them from being only a tool that provides the picture of why and how a programme works, to one that plays a role in embedding programmes within implementing organisations.

In resource-limited settings, there is increased demand for human immunodeficiency virus type 1 drug resistance testing. Because preservation of plasma specimens is often not feasible in resource-limited settings, use of dried blood spots (DBSs) is being adopted. We used 2 panels of DBSs for genotyping assay validation and proficiency testing in selected laboratories in the World Health Organization laboratory network in 14 countries. An amplification sensitivity of 1000 copies/mL was achieved by 2 laboratories. Reproducibility and accuracy of nucleotide sequence determination and resistance-associated mutation identification from DBSs was similar to that previously determined for plasma. International shipping at ambient temperature had no significant effect on amplification success. These studies indicate that DBS-based genotyping is equally reproducible and reliable, although slightly less sensitive, compared with plasma.

Breast tumor infiltrating lymphocytes (TIL) are enriched in tumor-specific cytotoxic T lymphocytes (CTL), and may represent a superior source of CTL compare to peripheral blood lymphocytes (PBL), for adoptive T cell immunotherapy of breast cancer. However, the immunocompetence of TIL and the possibility to consistently restore their tumor-specific lytic activity in vitro remains an open issue. In this study we evaluated the potential of tumor antigen-pulsed fully mature dendritic cell (DC) stimulation in restoring tumor-specific cytotoxicity in anergic TIL populations from advanced breast cancer patients. In addition we have compared tumor-specific T cell responses induced by tumor antigen-loaded DC stimulation of TIL to responses induced from PBL. Although TIL were consistently non-cytotoxic after isolation or culture in the presence of interleukin-2 (IL-2), in matched experiments from three consecutive patients, tumor-lysate-pulsed DC-stimulated CD8+ T cell derived from TIL were found to be significantly more cytotoxic than PBL (p < 0.05). In addition, cytotoxicity against autologous tumor cells was more significantly inhibited by an anti-HLA class I (W6/32) MAb in TIL compared to PBL (p < 0.05). CTL populations derived from TIL and PBL did not lyse autologous EBV-transformed lymphoblastoid cell lines, and showed negligible cytotoxicity against the NK-sensitive cell line K562. Furthermore, in both CD8+ T cell populations the majority of the tumor-specific CTL exhibited a Th1 cytokine bias (IFN-gamma(high)/IL-4(low)). Taken together, these data show that tumor lysate-pulsed mature DC can consistently restore tumor-specific lytic activity in non-cytotoxic breast cancer TIL. These results may have important implications for the treatment of chemotherapy resistant breast cancer with active or adoptive immunotherapy.