Background

Epidemiological studies evaluating the association between folate intake and risk of pancreatic cancer have produced inconsistent results. The statistical power to examine this association has been limited in previous studies partly because of small sample size and limited range of folate intake in some studies.

Methods

We analyzed primary data from 14 prospective cohort studies that included 319 716 men and 542 948 women to assess the association between folate intake and risk of pancreatic cancer. Folate intake was assessed through a validated food-frequency questionnaire at baseline in each study. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random effects model. All statistical tests were two-sided.

Results

During 7–20 years of follow-up across studies, 2195 pancreatic cancers were identified. No association was observed between folate intake and risk of pancreatic cancer in men and women (highest vs lowest quintile: dietary folate intake, pooled multivariable RR = 1.06, 95% CI = 0.90 to 1.25, Ptrend = .47; total folate intake [dietary folate and supplemental folic acid], pooled multivariable RR = 0.96, 95% CI = 0.80 to 1.16, Ptrend = .90). No between-study heterogeneity was observed (for dietary folate, Pheterogeneity = .15; for total folate, Pheterogeneity = .22).

Conclusion

Folate intake was not associated with overall risk of pancreatic cancer in this large pooled analysis.

The threat of prostate cancer (PC) and the significant and often negative impact of its treatment underscore the importance of prevention. High-grade prostatic intraepithelial neoplasia (HGPIN) has been identified as a potential premalignant lesion marking an increased risk of PC, and substantial evidence suggests that men with HGPIN are in need of PC prevention. In vitro, in vivo, epidemiologic, and clinical trial evidence that selenium supplementation protects against PC motivated the study we report here: A double-blind, randomized, placebo-controlled trial of selenium 200 (mcg/day) as selenomethionine in men with HGPIN. The primary endpoint was progression of HGPIN to PC over a three-year period. This NCI Intergroup trial was coordinated by the Southwest Oncology Group (SWOG). Of 619 enrolled patients, 423 randomized men with HGPIN (212, selenium; 211, placebo) were eligible (by central pathology review) and included in the primary analysis. Three-year cancer rates were 36.6% (placebo) versus 35.6% (selenium; P = 0.73, adjusted). The majority of patients who developed cancer on trial (70.8%, selenium, and 75.5%, placebo) had a Gleason score of ≤ 6; there were no differences in Gleason scores between the two arms. Subset analyses included the finding of a nonsignificantly reduced PC risk (relative risk = 0.82; 95% confidence interval, 0.40–1.69) in selenium versus placebo patients in the lowest quartile of baseline plasma selenium level (< 106 ng/ml). Overall, and in all other subsets defined by baseline blood selenium levels, selenium supplementation had no effect on PC risk. The 36% PC rate in men with HGPIN indicates the association of this lesion with an elevated PC risk. Future study in this setting should focus on selenium-deficient populations and selenium pharmacogenetics.

The recently published report of the SELECT evaluation of selenium and vitamin E provided strong evidence that selenium 200mcg/day in the form of selenomethionine does not protect selenium-replete men against prostate or any other cancer. This appears to refute the result of the much smaller Nutritional Prevention of Cancer (NPC) trial of selenium. Since SELECT did not test the NPC agent, is possible that the difference between the two trials stems partly from the use of different agents: selenomethionine in SELECT, selenized yeast in the NPC trial. One of the organic selenium forms suspected of having strong chemopreventive effects, and which may have been present in the NPC agent, is methyl selenocysteine. This study characterizes the single-dose pharmacokinetics of methyl selenocysteine.

Compliance with colorectal cancer screening recommendations requires considerable conscious effort on the part of the individual patient, making an individual's decisions about engagement in screening an important contributor to compliance or noncompliance. The objective of this paper was to examine the effectiveness of individual-level behavior theories and their associated constructs in accounting for engagement in colorectal cancer screening behavior. We reviewed the literature examining constructs from formal models of individual-level health behavior as factors associated with compliance with screening for colorectal cancer. All published studies examining one or more constructs from the health belief model, theory of planned behavior, transtheoretical model, or social cognitive theory and their relation to screening behavior or behavioral intentions were included in the analysis. By and large, results of studies supported the theory-based predictions for the influence of constructs on cancer screening behavior. However, the evidence base for many of these relations, especially for models other than the health belief model, is quite limited. Suggestions are made for future research on individual-level determinants of colorectal cancer screening.

Oncoprotein C-MYC is overexpressed in human metastatic melanomas and melanoma-derived cells where it is required for suppression of oncogene-induced senescence (OIS). The genetic events that maintain high levels of C-MYC in melanoma cells and their role in OIS are unknown. Here, we report that C-MYC in cells from several randomly chosen melanoma lines was up-regulated at the protein level, and largely due to the increased protein stability. Of all known regulators of C-MYC stability, levels of B56α subunit of the PP2A tumor suppressor complex were substantially suppressed in all human melanoma cells compared to normal melanocytes. Accordingly, immuno-histochemical analysis revealed that the lowest and the highest amounts of PP2A-B56α were predominantly detected in metastatic melanoma tissues and in primary melanomas from patients with good clinical outcome, respectively. Importantly, PP2A-B56α overexpression suppressed C-MYC in melanoma cells and induced OIS, whereas depletion of PP2A-B56α in normal human melanocytes up-regulated C-MYC protein levels and suppressed BRAFV600E- and, less efficiently, NRASQ61R-induced senescence. Our data reveal a mechanism of C-MYC overexpression in melanoma cells and identify a functional role for PP2A-B56α in OIS of melanocytic cells.

Despite the complexity and variability of decision processes, motor responses are generally stereotypical and independent of decision difficulty. How is this consistency achieved? Through an engineering analogy we consider how and why a system should be designed to realise not only flexible decision-making, but also consistent decision implementation. We specifically consider neurobiologically-plausible accumulator models of decision-making, in which decisions are made when a decision threshold is reached. To trade-off between the speed and accuracy of the decision in these models, one can either adjust the thresholds themselves or, equivalently, fix the thresholds and adjust baseline activation. Here we review how this equivalence can be implemented in such models. We then argue that manipulating baseline activation is preferable as it realises consistent decision implementation by ensuring consistency of motor inputs, summarise empirical evidence in support of this hypothesis, and suggest that it could be a general principle of decision making and implementation. Our goal is therefore to review how neurobiologically-plausible models of decision-making can manipulate speed-accuracy trade-offs using different mechanisms, to consider which of these mechanisms has more desirable decision-implementation properties, and then review the relevant neuroscientific data on which mechanism brains actually use.

Background

Pharmacies are venues in which patients seek out products and professional advice in order to improve overall health. However, many pharmacies in the United States continue to sell tobacco products, which are widely known to cause detrimental health effects. This conflict presents a challenge to pharmacists, who are becoming increasingly more involved in patient health promotion activities. This study sought to assess Western New York (WNY) area pharmacists’ opinions about the sale of tobacco products in pharmacies, and pharmacists’ opinions on their role in patient smoking cessation.

Methods

Participants responded to two parallel surveys; a web-based survey was completed by 148 university-affiliated pharmacist preceptors via a list based sample, and a mail-based survey was completed by the supervising pharmacist in 120 area pharmacies via a list-based sample. The combined response rate for both surveys was 31%. Univariate and bivariate analyses were performed to determine any significant differences between the preceptor and supervising pharmacist survey groups.

Results

Over 75% of respondents support legislation banning the sale of tobacco products in pharmacies. Over 86% of respondents would prefer to work in a pharmacy that does not sell tobacco products. Differences between preceptor and supervising pharmacist groups were observed. Action regarding counseling patients was uncommon among both groups.

Conclusions

Pharmacists support initiatives that increase their role in cessation counseling and initiatives that restrict the sale of tobacco products in pharmacies. These data could have important implications for communities and pharmacy practice.

The pay-it-forward reciprocity is a type of cooperative behavior that people who have benefited from others return favors to third parties other than the benefactors, thus pushing forward a cascade of kindness. The phenomenon of the pay-it-forward reciprocity is ubiquitous, yet how it evolves to be part of human sociality has not been fully understood. We develop an evolutionary dynamics model to investigate how network homophily influences the evolution of the pay-it-forward reciprocity. Manipulating the extent to which actors carrying the same behavioral trait are linked in networks, the computer simulation model shows that strong network homophily helps consolidate the adaptive advantage of cooperation, yet introducing some heterophily to the formation of network helps advance cooperation's scale further. Our model enriches the literature of inclusive fitness theory by demonstrating the conditions under which cooperation or reciprocity can be selected for in evolution when social interaction is not confined exclusively to relatives.

Background

A potential susceptibility locus for colorectal cancer on chromosome 9p24 (rs719725) was initially identified through a genome-wide association study, though replication attempts have been inconclusive.

Methods

We genotyped this locus and explored interactions with known risk factors as potential sources of heterogeneity, which may explain the previously inconsistent replication. We included Caucasians with colorectal adenoma or colorectal cancer and controls from four studies (total 3891 cases, 4490 controls): the Women’s Health Initiative (WHI); the Diet, Activity and Lifestyle Study (DALS); a Minnesota population-based case-control study (MinnCCS); and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). We used logistic regression to evaluate the association and test for gene-environment interactions.

Results

SNP rs719725 was statistically significantly associated with risk of colorectal cancer in WHI (OR per A allele 1.19; 95% CI 1.01–1.40; p-trend 0.04), marginally associated with adenoma risk in PLCO (OR per A allele 1.11; 95% CI 0.99–1.25; p-trend 0.07), and not associated in DALS and MinnCCS. Evaluating for gene-environment interactions yielded no consistent results across the studies. A meta-analysis of seventeen studies (including these four) gave an OR per A allele of 1.07 (95% CI 1.03–1.12; p-trend 0.001).

Conclusions

Our results suggest the A allele for SNP rs719725 at locus 9p24 is positively associated with a small increase in risk for colorectal tumors. Environmental risk factors for colorectal cancer do not appear to explain heterogeneity across studies.

Impact

If this finding is supported by further replication and functional studies, it may highlight new pathways underlying colorectal neoplasia.

The respective roles of knowledge and search have received considerable attention in the literature on expertise. However, most of the evidence on knowledge has been indirect – e.g., by inferring the presence of chunks in long-term memory from performance in memory recall tasks. Here we provide direct estimates of the amount of monochrestic (single use) and rote knowledge held by chess players of varying skill levels. From a large chess database, we analyzed 76,562 games played in 2008 by individuals ranging from Class B players (average players) to Masters to measure the extent to which players deviate from previously known initial sequences of moves (“openings”). Substantial differences were found in the number of moves known by players of different skill levels, with more expert players knowing more moves. Combined with assumptions independently made about the branching factor in master games, we estimate that masters have memorized about 100,000 opening moves. Our results support the hypothesis that monochrestic knowledge is essential for reaching high levels of expertise in chess. They provide a direct, quantitative estimate of the number of opening moves that players have to know to reach master level.

Background

The relationships between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk remain unresolved.

Methods

We investigated prospectively the association between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk in a pooled analysis of primary data from 13 cohort studies. Among 731 441 participants followed for up to 6–20 years, 5604 incident colon cancer case patients were identified. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random-effects model. All statistical tests were two-sided.

Results

Compared with nonconsumers, the pooled multivariable relative risks were 1.07 (95% CI = 0.89 to 1.30, Ptrend = .68) for coffee consumption greater than 1400 g/d (about six 8-oz cups) and 1.28 (95% CI = 1.02 to 1.61, Ptrend = .01) for tea consumption greater than 900 g/d (about four 8-oz cups). For sugar-sweetened carbonated soft drink consumption, the pooled multivariable relative risk comparing consumption greater than 550 g/d (about 18 oz) to nonconsumers was 0.94 (95% CI = 0.66 to 1.32, Ptrend = .91). No statistically significant between-studies heterogeneity was observed for the highest category of each beverage consumed (P > .20). The observed associations did not differ by sex, smoking status, alcohol consumption, body mass index, physical activity, or tumor site (P > .05).

Conclusions

Drinking coffee or sugar-sweetened carbonated soft drinks was not associated with colon cancer risk. However, a modest positive association with higher tea consumption is possible and requires further study.

Decision-making animals can use slow-but-accurate strategies, such as making multiple comparisons, or opt for simpler, faster strategies to find a ‘good enough’ option. Social animals make collective decisions about many group behaviours including foraging and migration. The key to the collective choice lies with individual behaviour. We present a case study of a collective decision-making process (house-hunting ants, Temnothorax albipennis), in which a previously proposed decision strategy involved both quality-dependent hesitancy and direct comparisons of nests by scouts. An alternative possible decision strategy is that scouting ants use a very simple quality-dependent threshold rule to decide whether to recruit nest-mates to a new site or search for alternatives. We use analytical and simulation modelling to demonstrate that this simple rule is sufficient to explain empirical patterns from three studies of collective decision-making in ants, and can account parsimoniously for apparent comparison by individuals and apparent hesitancy (recruitment latency) effects, when available nests differ strongly in quality. This highlights the need to carefully design experiments to detect individual comparison. We present empirical data strongly suggesting that best-of-n comparison is not used by individual ants, although individual sequential comparisons are not ruled out. However, by using a simple threshold rule, decision-making groups are able to effectively compare options, without relying on any form of direct comparison of alternatives by individuals. This parsimonious mechanism could promote collective rationality in group decision-making.

To be the fittest is central to proliferation in evolutionary games. Individuals thus adopt the strategies of better performing players in the hope of successful reproduction. In structured populations the array of those that are eligible to act as strategy sources is bounded to the immediate neighbors of each individual. But which one of these strategy sources should potentially be copied? Previous research dealt with this question either by selecting the fittest or by selecting one player uniformly at random. Here we introduce a parameter that interpolates between these two extreme options. Setting equal to zero returns the random selection of the opponent, while positive favor the fitter players. In addition, we divide the population into two groups. Players from group select their opponents as dictated by the parameter , while players from group do so randomly irrespective of . We denote the fraction of players contained in groups and by and , respectively. The two parameters and allow us to analyze in detail how aspirations in the context of the prisoner's dilemma game influence the evolution of cooperation. We find that for sufficiently positive values of there exist a robust intermediate for which cooperation thrives best. The robustness of this observation is tested against different levels of uncertainty in the strategy adoption process and for different interaction networks. We also provide complete phase diagrams depicting the dependence of the impact of and for different values of , and contrast the validity of our conclusions by means of an alternative model where individual aspiration levels are subject to evolution as well. Our study indicates that heterogeneity in aspirations may be key for the sustainability of cooperation in structured populations.

An important potential advantage of group-living that has been mostly neglected by life scientists is that individuals in animal groups may cope more effectively with unfamiliar situations. Social interaction can provide a solution to a cognitive problem that is not available to single individuals via two potential mechanisms: (i) individuals can aggregate information, thus augmenting their ‘collective cognition’, or (ii) interaction with conspecifics can allow individuals to follow specific ‘leaders’, those experts with information particularly relevant to the decision at hand. However, a-priori, theory-based expectations about which of these decision rules should be preferred are lacking. Using a set of simple models, we present theoretical conditions (involving group size, and diversity of individual information) under which groups should aggregate information, or follow an expert, when faced with a binary choice. We found that, in single-shot decisions, experts are almost always more accurate than the collective across a range of conditions. However, for repeated decisions – where individuals are able to consider the success of previous decision outcomes – the collective's aggregated information is almost always superior. The results improve our understanding of how social animals may process information and make decisions when accuracy is a key component of individual fitness, and provide a solid theoretical framework for future experimental tests where group size, diversity of individual information, and the repeatability of decisions can be measured and manipulated.

The problem of how to compromise between speed and accuracy in decision-making faces organisms at many levels of biological complexity. Striking parallels are evident between decision-making in primate brains and collective decision-making in social insect colonies: in both systems, separate populations accumulate evidence for alternative choices; when one population reaches a threshold, a decision is made for the corresponding alternative, and this threshold may be varied to compromise between the speed and the accuracy of decision-making. In primate decision-making, simple models of these processes have been shown, under certain parametrizations, to implement the statistically optimal procedure that minimizes decision time for any given error rate. In this paper, we adapt these same analysis techniques and apply them to new models of collective decision-making in social insect colonies. We show that social insect colonies may also be able to achieve statistically optimal collective decision-making in a very similar way to primate brains, via direct competition between evidence-accumulating populations. This optimality result makes testable predictions for how collective decision-making in social insects should be organized. Our approach also represents the first attempt to identify a common theoretical framework for the study of decision-making in diverse biological systems.

BACKGROUND

Coffee has been hypothesized to have pro- and anti-carcinogenic properties, while tea may contain anti-carcinogenic compounds. Studies assessing coffee intake and pancreatic cancer risk have yielded mixed results, while findings for tea intake have mostly been null. Sugar-sweetened carbonated soft drink (abbreviated as SSB) intake has been associated with higher circulating levels of insulin, which may promote carcinogenesis. Few prospective studies have examined SSB intake and pancreatic cancer risk; results have been heterogeneous.

METHODS

In this pooled analysis from 14 prospective cohort studies, 2,185 incident pancreatic cancer cases were identified among 853,894 individuals during follow-up. Multivariate (MV) study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and then pooled using a random effects model.

RESULTS

No statistically significant associations were observed between pancreatic cancer risk and intake of coffee (MVRR=1.10, 95% CI=0.81-1.48 comparing ≥900 to <0g/day; 237g≈8oz), tea (MVRR=0.96, 95% CI=0.78-1.16 comparing ≥400 to 0g/day; 237g≈8oz) or SSB (MVRR=1.19, 95% CI=0.98-1.46 comparing ≥250 to 0g/day; 355g≈12oz) (p-value, test for between-studies heterogeneity >0.05). These associations were consistent across levels of sex, smoking status and body mass index. When modeled as a continuous variable, a positive association was evident for SSB (MVRR=1.06, 95% CI=1.02-1.12).

CONCLUSION AND IMPACT

Overall, no associations were observed for intakes of coffee or tea during adulthood and pancreatic cancer risk. Although we were only able to examine modest intake of SSB, there was a suggestive, modest positive association for risk of pancreatic cancer for intakes of SSB.

The ability to predict the consequences of one's behavior in a particular environment is a mechanism for adaptation. In the absence of any cost to this activity, we might expect agents to choose behaviors that maximize their fitness, an example of directed innovation. This is in contrast to blind mutation, where the probability of becoming a new genotype is independent of the fitness of the new genotypes. Here, we show that under environments punctuated by rapid reversals, a system with both genetic and cultural inheritance should not always maximize fitness through directed innovation. This is because populations highly accurate at selecting the fittest innovations tend to over-fit the environment during its stable phase, to the point that a rapid environmental reversal can cause extinction. A less accurate population, on the other hand, can track long term trends in environmental change, keeping closer to the time-average of the environment. We use both analytical and agent-based models to explore when this mechanism is expected to occur.

Two recent case-control studies suggested that some flavonoid subgroups may play a role in preventing colorectal cancer. Previous prospective cohort studies generally reported no association; however, only a small subset of flavonoids was evaluated and partial flavonoid databases were used. We used the newly constructed U.S. Department of Agriculture flavonoid database to examine the association between consumption of total flavonoids, 6 flavonoid subgroups, and 29 individual flavonoids with adenomatous polyp recurrence in the Polyp Prevention Trial. The Polyp Prevention Trial was a randomized dietary intervention trial, which examined the effectiveness of a low-fat, high-fiber, high-fruit, and high-vegetable diet on adenoma recurrence. Intakes of flavonoids were estimated from a food frequency questionnaire. Multivariate logistic regression models (adjusted for age, body mass index, sex, regular non–steroidal anti-inflammatory use, and dietary fiber intake) were used to estimate odds ratios and 95% confidence intervals for both any and advanced adenoma recurrence within quartiles of energy-adjusted flavonoid intake (baseline, during the trial, and change during the trial). Total flavonoid intake was not associated with any or advanced adenoma recurrence. However, high intake of flavonols, which are at greater concentrations in beans, onions, apples, and tea, was associated with decreased risk of advanced adenoma recurrence (4th versus 1st quartile during the trial; odds ratio, 0.24; 95% confidence interval, 0.11, 0.53; Ptrend = 0.0006). Similar inverse associations were observed to a smaller extent for isoflavonoids, the flavonol kaempferol, and the isoflavonoids genistein and formononetin. Our data suggest that a flavonol-rich diet may decrease the risk of advanced adenoma recurrence.

Background

Reduced rank regression (RRR) has been used to identify dietary patterns that predict variation in a selected risk factor and may be useful in describing dietary exposures associated with glycemic index (GI) and glycemic load (GL).

Objective

To estimate breast cancer risk, we compared the relative utility of RRR-derived dietary patterns predictive of GI and GL with those of simple GI and GL.

Design

RRR was used to identify dietary patterns predicting GI and GL from food-frequency data obtained in the Western New York Exposure and Breast Cancer Study (1166 cases, 2105 controls). Odds ratios (ORs) and 95% CIs were estimated with unconditional logistic regression, adjusted for energy and nondietary breast cancer risk factors.

Results

Sweets, refined grains, and salty snacks explained 34% of the variance in GI and 68% of the variance in GL. In general, breast cancer risks were not associated with GI, GL, or dietary pattern score. However, we observed a significant reduction in postmenopausal breast cancer risk with GI and GL pattern scores combined (OR: 0.68; 95% CI: 0.50, 0.93), especially in women with a body mass index (in kg/m2) ≥25 (OR: 0.64; 95% CI: 0.44, 0.93). Conversely, in premenopausal women, increased risks were associated with high GL pattern scores only for women with a body mass index ≥25 (OR: 2.21; 95% CI: 1.04, 4.69).

Conclusions

Although RRR may be useful in studies of diet and disease, our results suggest that RRR dietary patterns based on GI and GL provide similar information regarding the association between breast cancer, GI, and GL.

Background

A previous clinical trial showed that selenium supplementation significantly reduced the incidence of prostate cancer. We report here a bioinformatics approach to gain new insights into selenium molecular targets that might be relevant to prostate cancer chemoprevention.

Materials and Methods

We first performed data mining analysis to identify genes which are consistently dysregulated in prostate cancer using published datasets from gene expression profiling of clinical prostate specimens. We then devised a method to systematically analyze three selenium microarray datasets from the LNCaP human prostate cancer cells, and to match the analysis to the cohort of genes implicated in prostate carcinogenesis. Moreover, we compared the selenium datasets with two datasets obtained from expression profiling of androgen-stimulated LNCaP cells.

Results

We found that selenium reverses the expression of genes implicated in prostate carcinogenesis. In addition, we found that selenium could counteract the effect of androgen on the expression of a subset obtained from androgen-regulated genes.

Conclusions

The above information provides us with a treasure of new clues to investigate the mechanism of selenium chemoprevention of prostate cancer. Furthermore, these selenium target genes could also serve as biomarkers in future clinical trials to gauge the efficacy of selenium intervention.

Epidemiologic studies of pancreatic cancer risk have reported null or non-significant positive associations for obesity, while associations for height have been null. Waist and hip circumference have been evaluated infrequently.

A pooled analysis of 14 cohort studies on 846,340 individuals was conducted; 2,135 individuals were diagnosed with pancreatic cancer during follow-up. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox proportional hazards models, and then pooled using a random effects model.

Compared to individuals with a body mass index (BMI) at baseline between 21–22.9kg/m2, pancreatic cancer risk was 47% higher (95%CI:23–75%) among obese (BMI≥30kg/m2) individuals. A positive association was observed for BMI in early adulthood (pooled multivariate [MV]RR = 1.30, 95%CI=1.09–1.56 comparing BMI≥25kg/m2 to a BMI between 21–22.9kg/m2). Compared to individuals who were not overweight in early adulthood (BMI<25kg/m2) and not obese at baseline (BMI<30kg/m2), pancreatic cancer risk was 54% higher (95%CI=24–93%) for those who were overweight in early adulthood and obese at baseline. We observed a 40% higher risk among individuals who had gained BMI ≥10kg/m2 between BMI at baseline and younger ages compared to individuals whose BMI remained stable. Results were either similar or slightly stronger among never smokers. A positive association was observed between waist to hip ratio (WHR) and pancreatic cancer risk (pooled MVRR=1.35 comparing the highest versus lowest quartile, 95%CI=1.03–1.78).

BMI and WHR were positively associated with pancreatic cancer risk. Maintaining normal body weight may offer a feasible approach to reducing morbidity and mortality from pancreatic cancer.

Empirical findings suggest that the mammalian brain has two decision-making systems that act at different speeds. We represent the faster system using standard signal detection theory. We represent the slower (but more accurate) cortical system as the integration of sensory evidence over time until a certain level of confidence is reached. We then consider how two such systems should be combined optimally for a range of information linkage mechanisms. We conclude with some performance predictions that will hold if our representation is realistic.

Many natural and artificial decision-making systems face decision problems where there is an inherent compromise between two or more objectives. One such common compromise is between the speed and accuracy of a decision. The ability to exploit the characteristics of a decision problem in order to vary between the extremes of making maximally rapid, or maximally accurate decisions, is a useful property of such systems. Colonies of the ant Temnothorax albipennis (formerly Leptothorax albipennis) are a paradigmatic decentralized decision-making system, and have been shown flexibly to compromise accuracy for speed when making decisions during house-hunting. During emigration, a colony must typically evaluate and choose between several possible alternative new nest sites of differing quality. In this paper, we examine this speed-accuracy trade-off through modelling, and conclude that noise and time-cost of assessing alternative choices are likely to be significant for T. albipennis. Noise and cost of such assessments are likely to mean that T. albipennis' decision-making mechanism is Pareto-optimal in one crucial regard; increasing the willingness of individuals to change their decisions cannot improve collective accuracy overall without impairing speed. We propose that a decentralized control algorithm based on this emigration behaviour may be derived for applications in engineering domains and specify the characteristics of the problems to which it should be suited, based on our new results.

Coevolution between ant colonies and their rare specialized parasites are intriguing, because lethal infections of workers may correspond to tolerable chronic diseases of colonies, but the parasite adaptations that allow stable coexistence with ants are virtually unknown. We explore the trade-offs experienced by Ophiocordyceps parasites manipulating ants into dying in nearby graveyards. We used field data from Brazil and Thailand to parameterize and fit a model for the growth rate of graveyards. We show that parasite pressure is much lower than the abundance of ant cadavers suggests and that hyperparasites often castrate Ophiocordyceps. However, once fruiting bodies become sexually mature they appear robust. Such parasite life-history traits are consistent with iteroparity– a reproductive strategy rarely considered in fungi. We discuss how tropical habitats with high biodiversity of hyperparasites and high spore mortality has likely been crucial for the evolution and maintenance of iteroparity in parasites with low dispersal potential.