Local gene transfer and expression following intramuscular administration of FGF-1 plasmid DNA in patients with critical limb ischemia

NV1FGF is an expression plasmid encoding sp.FGF-1(21-154) currently under investigation for therapeutic angiogenesis in clinical trials. NV1FGF plasmid distribution and transgene expression following intramuscular (IM) injection in patients is unknown. The study involved six patients with chronic critical limb ischemia (CLI) planned to undergo amputation. A total dose of 0.5, 2, or 4 mg NV1FGF was administered as eight IM injections (0.006, 0.25, or 0.5 mg per injection) 3-5 days before amputation. Injected sites (30 cm(3)) were divided into equally sized smaller pieces to assess spatial distribution of NV1FGF sequences (PCR), NV1FGF mRNA (reverse transcriptase-PCR), and fibroblast growth factor-1 (FGF-1)-expressing cells (immunohistochemistry). Data indicated gene expression at all doses. The distribution area was within 5-12 cm for NV1FGF sequences containing the expression cassette, up to 5 cm for NV1FGF mRNA, and up to 3 cm for FGF-1-expressing myofibers. All FGF receptors were detected indicating robust potential for bioactivity after NV1FGF gene transfer. Circulating levels of NV1FGF sequences were shown to decrease within days after injection. Data support demonstration of plasmid-mediated gene transfer and expression in muscles from patients with CLI. FGF-1 expression was shown to be limited to injection sites, which supports the concept of multiple-site injection for therapeutic use.

Quantifying entrepreneurship and its impact on local economic performance: A spatial assessment in rural Switzerland

Regional and rural development policies in Europe increasingly emphasize entrepreneurship to mobilize the endogenous economic potential of rural territories. This study develops a concept to quantify entrepreneurship as place-dependent local potential to examine its impact on the local economic performance of rural territories in Switzerland. The short-to-medium-term impact of entrepreneurship on the economic performance of 1706 rural municipalities in Switzerland is assessed by applying three spatial random effects models. Results suggest a generally positive relationship between entrepreneurship and local development: rural municipalities with higher entrepreneurial potential generally show higher business tax revenues per capita and a lower share of social welfare cases among the population, although the impact on local employment is less clear. The explanatory power of entrepreneurship in all three models, however, was only moderate. This finding suggests that political expectations of fostering entrepreneurship to boost endogenous rural development in the short-to-medium term should be damped.

Signal Processing for the Measurement of the Deuterium/Hydrogen Ratio in the Local Interstellar Medium

We report on a comprehensive signal processing procedure for very low signal levels for the measurement of neutral deuterium in the local interstellar medium from a spacecraft in Earth orbit. The deuterium measurements were performed with the IBEX-Lo camera on NASA’s Interstellar Boundary Explorer (IBEX) satellite. Our analysis technique for these data consists of creating a mass relation in three-dimensional time of flight space to accurately determine the position of the predicted D events, to precisely model the tail of the H events in the region where the H tail events are near the expected D events, and then to separate the H tail from the observations to extract the very faint D signal. This interstellar D signal, which is expected to be a few counts per year, is extracted from a strong terrestrial background signal, consisting of sputter products from the sensor’s conversion surface. As reference we accurately measure the terrestrial D/H ratio in these sputtered products and then discriminate this terrestrial background source. During the three years of the mission time when the deuterium signal was visible to IBEX, the observation geometry and orbit allowed for a total observation time of 115.3 days. Because of the spinning of the spacecraft and the stepping through eight energy channels the actual observing time of the interstellar wind was only 1.44 days. With the optimised data analysis we found three counts that could be attributed to interstellar deuterium. These results update our earlier work.

Distribución social de los conocimientos de medicina tradicional en los Andes: Estudios de caso de Perú y Bolivia

Los factores socio-económicos que influyen sobre los conocimientos de plantas medicinales de la población (personas no especialistas que se auto medican con plantas medicinales) han sido poco estudiado en la investigación etnobotánica. En este marco, el objetivo del trabajo de investigación fue analizar la distribución social del conocimiento sobre plantas medicinales en comunidades rurales de los Andes peruanos y bolivianos. Se realizaron entrevistas detalladas y ejercicios de listados libres en idioma Quechua con la ayuda de un intérprete local con 18 familias de un distrito rural de los Andes peruanos y 18 familias de una subcentral rural de los Andes bolivianos. Se recolectaron muestras botánicas de las plantas junto con los informantes en las dos áreas de estudios de caso. Un análisis cuantitativo de clasificación mostró que, en los dos estudios de caso, los vínculos de parentesco y la historia personal influye sobre las especies de plantas conocidas y usadas, en vez de otros factores como la edad, el nivel de educación, el estatuto socio-económico o la religión. El proceso de migración hacía los centros urbanos y las tierras bajas amazónicas, generalmente considerado como un factor importante en la pérdida de los conocimientos de medicina tradicional, solo tiene un impacto sobre el conocimiento de la población en el caso de familias que migran más de seis meses por año o de manera permanente. La migración no influye sobre los niveles de conocimientos de plantas medicinales ni sobre las estrategias terapéuticas de las familias que migran de forma temporal o por periodos más cortos de tiempo. Se demuestra que el impacto de factores socio-económicos externos que son generalmente considerados como la causa de la pérdida de los conocimientos de medicina tradicional en las altas tierras andinas es limitado. Además, los resultados de investigación implican que en zonas rurales donde la migración tiene un impacto sobre los conocimientos locales, la medicina tradicional podría ser mejor fortalecida si se trabaja estrechamente con familias y su red de parentesco extendida.

Long-term results of therapeutic local anesthesia (neural therapy) in 280 referred refractory chronic pain patients

BACKGROUND: Can the application of local anesthetics (Neural Therapy, NT) alone durably improve pain symptoms in referred patients with chronic and refractory pain? If the application of local anesthetics does lead to an improvement that far exceeds the duration of action of local anesthetics, we will postulate that a vicious circle of pain in the reflex arcs has been disrupted (hypothesis). METHODS: Case series design. We exclusively used procaine or lidocaine. The inclusion criteria were severe pain and chronic duration of more than three months, pain unresponsive to conventional medical measures, written referral from physicians or doctors of chiropractic explicitly to NT. Patients with improvement of pain who started on additional therapy during the study period for a reason other than pain were excluded in order to avoid a potential bias. Treatment success was measured after one year follow-up using the outcome measures of pain and analgesics intake. RESULTS: 280 chronic pain patients were included; the most common reason for referral was back pain. The average number of consultations per patient was 9.2 in the first year (median 8.0). After one year, in 60 patients pain was unchanged, 52 patients reported a slight improvement, 126 were considerably better, and 41 pain-free. At the same time, 74.1 % of the patients who took analgesics before starting NT needed less or no more analgesics at all. No adverse effects or complications were observed. CONCLUSIONS: The good long-term results of the targeted therapeutic local anesthesia (NT) in the most problematic group of chronic pain patients (unresponsive to all evidence based conventional treatment options) indicate that a vicious circle has been broken. The specific contribution of the intervention to these results cannot be determined. The low costs of local anesthetics, the small number of consultations needed, the reduced intake of analgesics, and the lack of adverse effects also suggest the practicality and cost-effectiveness of this kind of treatment. Controlled trials to evaluate the true effect of NT are needed.

Apoyando innovaciones locales: Un instrumento para el fortalecimiento de innovaciones locales y la promoción del desarrollo rural sostenible: Experiencias de dos talleres pilotos de MASAL y CDE realizados en laprovincia de Cuzco, Perú

Local communities have often underestimated their endogenous potentials for innovation – potentials that could help them adapt to changing socio-cultural, political, economic and environmental conditions, to improve their livelihoods, develop their own visions, and negotiate their own priorities. While the significance of local innovation potentials for sustainable development is now increasingly acknowledged, projects and development plans rarely attempt to explicitly develop these potentials; nor do they try to disseminate local innovations within and among communities. Based on the conceptual framework of “social learning”, CDE has developed an instrument to promote existing local potential for innovation. The instrument is based on social learning processes involving different stakeholder groups in local contexts. It was successfully tested during two pilot workshops in a rural development context in the Peruvian highland. The present paper reports on the experience of these two workshops held in April and May 2004 in the communities of Tungasuca in the Cuzco Province. The paper describes the context of innovations and the methodology applied, followed by a detailed description of the contents and outcomes of the workshops, as well as the experience gained in the process. Finally it draws a set of conclusions and presents the lessons learnt.