A phase II study of active specific immunotherapy and5-FU/Leucovorin as adjuvant therapy for stage III colon carcinoma

Active specific immunotherapy, using vaccines with autologous tumour cells and BCG, significantly reduces the rate of tumour recurrence in stage II colon cancer patients, while no clinical benefit has yet been observed in stage III patients. Adjuvant treatment with 5-Fluorouracil/Leucovorin is now considered standard therapy for stage III colon carcinoma and results in an absolute survival benefit of approximately 10%. Yet, the 5-year overall survival rate of stage III colon cancer patients is only 40–50%. Combining chemotherapy and immunotherapy might improve prognosis for stage III patients, especially when considering that active specific immunotherapy and chemotherapy have shown synergistic effects in pre-clinical tumour models. We performed a phase II study with 56 patients, using the combination of active specific immunotherapy and chemotherapy as an adjuvant therapy in stage III colon cancer patients to assess the influence of 5-Fluorouracil/Leucovorin on anti-tumour immunity induced by autologous tumour cell vaccinations. Anti-tumour immunity was measured before and after chemotherapy by means of delayed type hypersensitivity reactions, taken 48 h after the third and the fourth vaccination. We also investigated the toxicity of this combined immuno-chemotherapy treatment. Delayed type hypersensitivity reactions before chemotherapy had a median size of 20.3 mm, while after chemotherapy delayed type hypersensitivity size was 18.4 mm (P=0.01), indicating that chemotherapy hardly affected anti-tumour immunity. The severity of ulcers at the BCG vaccination sites was comparable to previous studies. In 30% of the patients grade III or grade IV chemotherapy related toxicity was seen; this is comparable to what is normally observed after adjuvant chemotherapy alone. This study shows that the active specific immunotherapy-induced anti-tumour immune response is only minimally impaired by consecutive chemotherapy and that the combined treatment of stage III colon cancer patients with active specific immunotherapy and 5-Fluorouracil/Leucovorin does not cause unexpected toxicity

Cosmic ray diffusion near the Bohm limit in the Cassiopeia A supernova remnant

Supernova remnants (SNRs) are believed to be the primary location of the acceleration of Galactic cosmic rays, via diffusive shock (Fermi) acceleration. Despite considerable theoretical work the precise details are still unknown, in part because of the difficulty in directly observing nucleons that are accelerated to TeV energies in, and affect the structure of, the SNR shocks. However, for the last ten years, X-ray observatories ASCA, and more recently Chandra, XMM-Newton, and Suzaku have made it possible to image the synchrotron emission at keV energies produced by cosmic-ray electrons accelerated in the SNR shocks. In this article, we describe a spatially-resolved spectroscopic analysis of Chandra observations of the Galactic SNR Cassiopeia A to map the cutoff frequencies of electrons accelerated in the forward shock. We set upper limits on the electron diffusion coefficient and find locations where particles appear to be accelerated nearly as fast as theoretically possible (the Bohm limit).Comment: 18 pages, 5 figures. Accepted for publication in Nature Physics (DOI below), final version available week of August 28, 2006 at http://www.nature.com/nphy

The Timing of the Cognitive Cycle

We propose that human cognition consists of cascading cycles of recurring brain events. Each cognitive cycle senses the current situation, interprets it with reference to ongoing goals, and then selects an internal or external action in response. While most aspects of the cognitive cycle are unconscious, each cycle also yields a momentary “ignition” of conscious broadcasting. Neuroscientists have independently proposed ideas similar to the cognitive cycle, the fundamental hypothesis of the LIDA model of cognition. High-level cognition, such as deliberation, planning, etc., is typically enabled by multiple cognitive cycles. In this paper we describe a timing model LIDA's cognitive cycle. Based on empirical and simulation data we propose that an initial phase of perception (stimulus recognition) occurs 80–100 ms from stimulus onset under optimal conditions. It is followed by a conscious episode (broadcast) 200–280 ms after stimulus onset, and an action selection phase 60–110 ms from the start of the conscious phase. One cognitive cycle would therefore take 260–390 ms. The LIDA timing model is consistent with brain evidence indicating a fundamental role for a theta-gamma wave, spreading forward from sensory cortices to rostral corticothalamic regions. This posteriofrontal theta-gamma wave may be experienced as a conscious perceptual event starting at 200–280 ms post stimulus. The action selection component of the cycle is proposed to involve frontal, striatal and cerebellar regions. Thus the cycle is inherently recurrent, as the anatomy of the thalamocortical system suggests. The LIDA model fits a large body of cognitive and neuroscientific evidence. Finally, we describe two LIDA-based software agents: the LIDA Reaction Time agent that simulates human performance in a simple reaction time task, and the LIDA Allport agent which models phenomenal simultaneity within timeframes comparable to human subjects. While there are many models of reaction time performance, these results fall naturally out of a biologically and computationally plausible cognitive architecture

Определение скорости перемещения деформаций растяжений в массиве при подземной выемке угля

Приведена швидкість переміщення деформацій в непорушеному масиві. Встановлено, що швидкість в породах середнього ступеня метаморфізму складає 15 м/добу. Середня швидкість переміщення деформацій в сланцях – 10 м/добу, в піщаниках – 15 м/добу. При повторній підробці швидкість переміщення деформацій складає 17 м/добу.Deformation’s speed travel in the virgin rock massif is given in this article. It has been determined that deformation’s speed in the rocks of medium-scale metamorphism was 15 meters over the entire circadian period. The average speed of deformation’s travel in the shale rocks is 10 meters over the entire circadian period and in the sandstone is 15 meters over the entire circadian period. During the recurring undermining the speed travel of deformations is 17 meters over the entire circadian period

Epidemiology of acute and chronic hepatitis B virus infection in Norway, 1992-2009

<p>Abstract</p> <p>Background</p> <p>Norway is classified as a low prevalence country for hepatitis B virus infection. Vaccination is only recommended for risk groups (intravenous drug users (IDUs), Men who have Sex with Men (MSM), immigrants and contacts of known carriers). We describe the epidemiology of reported cases of hepatitis B in Norway, during the years 1992-2009 in order to assess the validity of current risk groups and recommend preventive measures.</p> <p>Methods</p> <p>We used case based data from the national surveillance system on acute and chronic hepatitis B. The Norwegian Statistics Bureau provided population and migration data and the Norwegian Institute for Alcohol and Drug Research the estimated number of active IDUs between 2002-2007. Incidence rates (IR) and incidence rate ratios (IRR) for acute hepatitis B and notification rates (NR) and notification rate ratios (NRR) for chronic hepatitis B with 95% confidence intervals were calculated.</p> <p>Results</p> <p>The annual IR of acute hepatitis B ranged from 0.7/100,000 (1992) to 10.6/100,000 (1999). Transmission occurred mainly among IDUs (64%) or through sexual contact (24%). The risk of acquiring acute hepatitis B was highest in people aged 20-29 (IRR = 6.6 [3.3-13.3]), and in males (IRR = 2.4 [1.7-3.3]). We observed two peaks of newly reported chronic hepatitis B cases in 2003 and 2009 (NR = 17.6/100,000 and 17.4/100,000, respectively). Chronic hepatitis B was more likely to be diagnosed among immigrants than among Norwegians (NRR = 93 [71.9-120.6]), and among those 20-29 compared to those 50-59 (NRR = 5.2 [3.5-7.9]).</p> <p>Conclusions</p> <p>IDUs remain the largest risk group for acute hepatitis B. The observed peaks of chronic hepatitis B are related to increased immigration from high endemic countries and screening and vaccination of these groups is important to prevent further spread of infection. Universal screening of pregnant women should be introduced. A universal vaccination strategy should be considered, given the high cost of reaching the target populations. We recommend evaluating the surveillance system for hepatitis B as well as the effectiveness of screening and vaccinating immigrant populations.</p

Concepts of Animal Health and Welfare in Organic Livestock Systems

In 2005, The International Federation of Organic Agricultural Movements (IFOAM) developed four new ethical principles of organic agriculture to guide its future development: the principles of health, ecology, care, and fairness. The key distinctive concept of animal welfare in organic agriculture combines naturalness and human care, and can be linked meaningfully with these principles. In practice, a number of challenges are connected with making organic livestock systems work. These challenges are particularly dominant in immature agro-ecological systems, for example those that are characterized by industrialization and monoculture. Some of the current challenges are partly created by shortages of land and manure, which encourage zero-grazing and other confined systems. Other challenges are created in part by the conditions for farming and the way in which global food distribution systems are organized, e.g., how live animals are transported, how feed is traded and transported all over the globe, and the development of infrastructure and large herds. We find that the overall organic principles should be included when formulating guidelines for practical organic animal farming. This article explores how the special organic conceptions of animal welfare are related to the overall principles of organic agriculture. The aim is to identify potential routes for future development of organic livestock systems in different contexts and with reference to the specific understanding of animal welfare in organic agriculture. We include two contrasting cases represented by organic livestock systems in northwestern Europe and farming systems in tropical low-income countries; we use these cases to explore the widely different challenges of organic livestock systems in different parts of the world