Extending a biologically inspired model of choice: multi-alternatives, nonlinearity and value-based multidimensional choice

The leaky competing accumulator (LCA) is a biologically inspired model of choice. It describes the processes of leaky accumulation and competition observed in neuronal populations during choice tasks and it accounts for reaction time distributions observed in psychophysical experiments. This paper discusses recent analyses and extensions of the LCA model. First, it reviews the dynamics and examines the conditions that make the model achieve optimal performance. Second, it shows that nonlinearities of the type present in biological neurons improve performance when the number of choice alternatives increases. Third, the model is extended to value-based choice, where it is shown that nonlinearities in the value function explain risk aversion in risky choice and preference reversals in choice between alternatives characterized across multiple dimensions.     

The Jenner bicentenary: the introduction and early distribution of smallpox vaccine

Abstract This review describes the background to Jenner's first vaccination, his later work, and the dissemination of information about vaccination and the vaccine itself. Although based on relatively slender evidence, Jenner's theories were basically sound and he merits the credit given him. Given the circumstances, particularly the slow speed of travel and the lack of information about the duration of immunity, vaccination became established very quickly in many countries.     

应用微量滴定法测定天花疫苗效力

微量滴定法代替血球吸附法测定天花疫苗效力。通过对Vero细胞接种浓度和细胞病变判定时间的优化,确定了微量滴定法测定天花疫苗效力的方法,用Vero细胞微量滴定法和血球吸附法测定14批天花疫苗。两种滴定方法的检测结果差异有显著意义(P<0.05),二者存在正相关(r=0.76,0.001相似文献   

HLA alleles associated with the adaptive immune response to smallpox vaccine: a replication study

We previously reported HLA allelic associations with vaccinia virus (VACV)-induced adaptive immune responses in a cohort of healthy individuals (n = 1,071 subjects) after a single dose of the licensed smallpox (Dryvax) vaccine. This study demonstrated that specific HLA alleles were significantly associated with VACV-induced neutralizing antibody (NA) titers (HLA-B*13:02, *38:02, *44:03, *48:01, and HLA-DQB1*03:02, *06:04) and cytokine (HLA-DRB1*01:03, *03:01, *10:01, *13:01, *15:01) immune responses. We undertook an independent study of 1,053 healthy individuals and examined associations between HLA alleles and measures of adaptive immunity after a single dose of Dryvax-derived ACAM2000 vaccine to evaluate previously discovered HLA allelic associations from the Dryvax study and determine if these associations are replicated with ACAM2000. Females had significantly higher NA titers than male subjects in both study cohorts [median ID50 discovery cohort 159 (93, 256) vs. 125 (75, 186), p < 0.001; replication cohort 144 (82, 204) vs. 110 (61, 189), p = 0.024]. The association between the DQB1*03:02 allele (median ID₅₀ discovery cohort 152, p = 0.015; replication cohort 134, p = 0.010) and higher NA titers was replicated. Two HLA associations of comparable magnitudes were consistently found between DRB1*04:03 and DRB1*08:01 alleles and IFN-γ ELISPOT responses. The association between the DRB1*15:01 allele with IFN-γ secretion was also replicated (median pg/mL discovery cohort 182, p = 0.052; replication cohort 203, p = 0.014). Our results suggest that smallpox vaccine-induced adaptive immune responses are significantly influenced by HLA gene polymorphisms. These data provide information for functional studies and design of novel candidate smallpox vaccines.     

Pathomorphological and immunofluorescent studies of smallpox vaccine neurotropism]

Experiments were conducted on guinea pigs sensitized with the AK C-vaccine components. In intracardiac injection with smallpox vaccine there was shown a possibility of development of marked hemodynamic disturbances, of the inflammatory-dystrophic processes of irreversibel character, with a subsequent neuronophagia and demyelinization. Injection of smallpox vaccine into the circulation of intact guinea pigs was accompanied by development in the nervous system of insignificant circulatory disturbances and of the inflammatory dystrophic phenomena of reversible character. A method of immunofluorescence was used and the antigen of the vaccine virus was revealed in the neurons of the brain and the spinal cord of the sensitized and intact animals. Marked hemodynamic and insignificant inflammatory-dystrophic processes were revealed in the nervous system of a child which died of the post-vaccinal encephalitis; an antigen of the smallpox virus was found by the immunofluorescent method in the nerve cells and the vessels in various portions of the nervous system.     

Simulation of multidimensional community patterns: towards a comprehensive model

Ecological gradients in the field layer of southern boreal forests in South Finland were studied in relation to the dominant tree species and the age of forest stands. The data are from a systematic sample of 529 plots from an area of 150 × 200 km, collected in the Third National Forest Inventory in 1951–53. Detrended correspondence analysis (DCA) was applied to log-transformed species cover values. It revealed three main gradients: fertility, moisture, and the effect of cattle grazing in forests (still extensive in the early 1950's). The fertility gradient dominated the first axis and the two latter sources of variation confounded with it in a complex manner in the first two axes of DCA. The second DCA axis was associated with canopy effects on understory pattern, with Pinus and Picea having opposite and Betula intermediate effects. These results were compared with an ordination model of Cajander's forest site types, based on DCA of independent, ideal data of 107 indicator species. The fertility gradient recovered by the model was almost identical to that obtained from the field data. The gradient was also stable from intermediate-age (40–69 yrold) to older forests. The forest site types showed rather large overlaps with main neighbouring types in composition of ground vegetation or nutrient status of the humus. Competitively efficient feather-mosses, which are dependent on nutrients released from the tree crowns, are considered important regulators of the understory vegetation. Accordingly, alternative approaches to the forest site type classification to be used in boreal forests treated by modern intensive forestry should give more weight to the effect of the canopy trees.     

Effects of behavioral changes in a smallpox attack model

The impact of individual and community behavioral changes in response to an outbreak of a disease with high mortality is often not appreciated. Response strategies to a smallpox bioterrorist attack have focused on interventions such as isolation of infectives, contact tracing, quarantine of contacts, ring vaccination, and mass vaccination. We formulate and analyze a mathematical model in which some individuals lower their daily contact activity rates once an epidemic has been identified in a community. Transmission parameters are estimated from data and an expression is derived for the effective reproduction number. We use computer simulations to analyze the effects of behavior change alone and in combination with other control measures. We demonstrate that the spread of the disease is highly sensitive to how rapidly people reduce their contact activity rates and to the precautions that the population takes to reduce the transmission of the disease. Even gradual and mild behavioral changes can have a dramatic impact in slowing an epidemic. When behavioral changes are combined with other interventions, the epidemic is shortened and the number of smallpox cases is reduced. We conclude that for simulations of a smallpox outbreak to be useful, they must consider the impact of behavioral changes. This is especially true if the model predictions are being used to guide public health policy.     

Clonal vaccinia virus grown in cell culture as a new smallpox vaccine

Although the smallpox virus was eradicated over 20 years ago, its potential release through bioterrorism has generated renewed interest in vaccination. To develop a modern smallpox vaccine, we have adapted vaccinia virus that was derived from the existing Dryvax vaccine for growth in a human diploid cell line. We characterized six cloned and one uncloned vaccine candidates. One clone, designated ACAM1000, was chosen for development based on its comparability to Dryvax when tested in mice, rabbits and monkeys for virulence and immunogenicity. By most measures, ACAM1000 was less virulent than Dryvax. We compared ACAM1000 and Dryvax in a randomized, double-blind human clinical study. The vaccines were equivalent in their ability to produce major cutaneous reactions ('takes') and to induce neutralizing antibody and cell-mediated immunity against vaccinia virus.