Intratumoral Delivery of Plasmid Interleukin-12 Via Electroporation Leads to Regression of Injected and Non-Injected Tumors in Merkel Cell Carcinoma

Purpose: Interleukin-12 (IL12) promotes adaptive type I immunity and has demonstrated antitumor efficacy, but systemic administration leads to severe adverse events (AE), including death. This pilot trial investigated safety, efficacy, and immunologic activity of intratumoral delivery of IL12 plasmid DNA (tavo) via in vivo electroporation (i.t.-tavo-EP) in patients with Merkel cell carcinoma (MCC), an aggressive virus-associated skin cancer. Experimental Design: Fifteen patients with MCC with superficial injectable tumor(s) received i.t.-tavo-EP on days 1, 5, and 8 of each cycle. Patients with locoregional MCC (cohort A, N = 3) received one cycle before definitive surgery in week 4. Patients with metastatic MCC (cohort B, N = 12) received up to four cycles total, administered at least 6 weeks apart. Serial tumor and blood samples were collected. Results: All patients successfully completed at least one cycle with transient, mild (grades 1 and 2) AEs and without significant systemic toxicity. Sustained (day 22) intratumoral expression of IL12 protein was observed along with local inflammation and increased tumor-specific CD8+ T-cell infiltration, which led to systemic immunologic and clinical responses. The overall response rate was 25% (3/12) in cohort B, with 2 patients experiencing durable clinical benefit (16 and 55+ months, respectively). Two cohort A patients (1 with pathologic complete remission) were recurrence-free at 44+ and 75+ months. Conclusions: I.t.-tavo-EP was safe and feasible without systemic toxicity. Sustained local expression of IL12 protein and local inflammation led to systemic immune responses and clinically meaningful benefit in some patients. Gene electrotransfer, specifically i.t.-tavo-EP, warrants further investigation for immunotherapy of cancer

Immigration and Internal Migration 'Flight' from US Metropolitan Areas: Toward a New Demographic Balkanisation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68704/2/10.1080_00420989550012861.pd

Density and community structure of soil- and bark-dwelling microarthropods along an altitudinal gradient in a tropical montane rainforest

Microarthropod communities in the soil and on the bark of trees were investigated along an elevation gradient (1,850, 2,000, 2,150, 2,300 m) in a tropical montane rain forest in southern Ecuador. We hypothesised that the density of microarthropods declines with depth in soil and increases with increasing altitude mainly due to the availability of resources, i.e. organic matter. In addition, we expected bark and soil communities to differ strongly, since the bark of trees is more exposed to harsher factors. In contrast to our hypothesis, the density of major microarthropod groups (Collembola, Oribatida, Gamasina, Uropodina) was generally low and decreased with altitude. However, as we predicted the density of each of the groups decreased with soil depth. Density of microarthropods on tree bark was lower than in soil. Overall, 43 species of oribatid mites were found, with the most abundant higher taxa being Poronota, pycnonotic Apheredermata, Mixonomata and Eupheredermata. The oribatid mite community on bark did not differ significantly from that in soil. The number of oribatid mite species declined with altitude (24, 23, 17 and 13 species at 1,850, 2,000, 2,150 and 2,300 m, respectively). Rarefaction curves indicate that overall about 50 oribatid mite species are to be expected along the studied altitudinal gradient. Results of this study indicate (1) that microarthropods may be limited by the quality of resources at high altitudes and by the amount of resources at deeper soil layers, and (2) that the bark of trees and the soil are habitats of similar quality for oribatid mites

Opportunities and Challenges in Providing Health Care for International Retirement Migrants: A Qualitative Case Study of Canadians Travelling To Yuma, Arizona

Background Increasing numbers of older individuals opt to spend extended time abroad each year for lifestyle, health, and financial reasons. This practice is known as international retirement migration, and it is particularly popular among retirees in Global North countries such as Canada. Despite the popularity of international retirement migration, very little is known about how and why health care is accessed while abroad, nor the opportunities and challenges posed for destination hospitals. In this article we focus on addressing the latter knowledge gap. Methods This qualitative case study is focused on the only hospital in Yuma, Arizona – a popular destination for Canadian retirement migrants in the United States. We conducted focus groups with workers at this hospital to explore their experiences of treating this transnational patient group. Twenty-seven people participated in three, 90-min focus groups: twelve nurses, six physicians, and nine administrators. Thematic analysis of the focus group transcripts was conducted using a triangulated approach. Results Participants identified three care environments: practice, transnational, and community. Each environment presents specific opportunities and challenges pertaining to treating Canadian retirement migrants. Important opportunities include the creation of a strong and diverse seasonal workforce in the hospital, new transnational paths of communication and information sharing for physicians and health administrators, and informal care networks that support formal health care services within and beyond the hospital. These opportunities are balanced out by billing, practical, administrative, and lifestyle-related challenges which add complexity to treating this group of transnational patients. Conclusion Canadians represent a significant group of patients treated in Yuma, Arizona. This is contrary to long-standing, existing research that depicts older Canadians as being reluctant to access care while in the United States. Significant overlaps exist between the opportunities and challenges in the practice, transnational and community environments. More research is needed to better understand if these findings are similar to other destinations popular with Canadian international retirement migrants or if they are unique to Yuma, Arizona

A medium-spatial scale distribution pattern of pseudoscorpionida (arachnida) in a gradient of topography (altitude and inclination), soil factors, and litter in a central Amazonia forest reserve, Brazil

In Amazonia, nothing is known about the distribution of the invertebrates on a medium-spatial scale pattern. In a trail system of 64 km2 at Ducke Reserve, we sampled 72 transects using the hand-sorting method and Berlese-Tullgren extraction. The reserve possesses ecosystems of "terra-firme" forest and the trail system represents a gradient of topographic soil factors and vegetation, avoiding categorizations. Considering the abundance and diversity of Pseudoscorpionida, we investigated the relation of the community to environmental factors tested (topography, clay percentage, litter, and soil pH), to the two major drainage basins of the reserve, and if these invertebrates can be used as biological indicators to monitor changes. We registered two species for the first time in the reserve, increasing the known diversity to 17 species. The lack of correlation with the predictor variables and the large home range, indicate that pseudoscorpions are not good biological indicators in the reserve. As the eastern and western watersheds are not separate management units for the community, our results show that they are generalist predators. In spite of our results and lack of knowledge concerning their biology, life history and taxonomy, pseudoscorpions are cosmopolitan and easy to find and measure. Compared with previous studies in the reserve, they have a consistent pattern of abundance and diversity throughout the years showing the stability of the community which can be checked mainly by comparison with environmental changes that would occur in the reserve. An investigation on a medium-spatial scale pattern and over a long-term period including other habitats, and also other predictor variables, like humidity, the structure of the vegetation and canopy closure, will be necessary to reinforce the observed tendencies

Reconsidering the Carnap-Kuhn Connection

Recently, some philosophers of science (e.g., Gürol Irzik, Michael Friedman) have challenged the ‘received view’ on the relationship between Rudolf Carnap and Thomas Kuhn, suggesting that there is a close affinity (rather than opposition) between their philosophical views. In support of this argument, these authors cite Carnap and Kuhn’s similar views on incommensurability, theory-choice, and scientific revolutions. Against this revisionist view, I argue that the philosophical relationship between Carnap and Kuhn should be regarded as opposed rather than complementary. In particular, I argue that a consideration of the fundamentally disparate nature of the broader philosophical projects of Carnap (logic of science) and Kuhn (providing a theory of scientific revolutions)renders the alleged similarities between their views superficial in comparison to their fundamental differences. In defense of the received view, I suggest that Carnap and Kuhn are model representatives of two contrasting styles of doing philosophy of science, viz., logical analysis and historical analysis respectively. This analysis clarifies the role played by Kuhn’s Structure of Scientific Revolutions in the demise of logical empiricism in the second half of the twentieth-century