The successor representation in human reinforcement learning.

Theories of reward learning in neuroscience have focused on two families of algorithms thought to capture deliberative versus habitual choice. 'Model-based' algorithms compute the value of candidate actions from scratch, whereas 'model-free' algorithms make choice more efficient but less flexible by storing pre-computed action values. We examine an intermediate algorithmic family, the successor representation, which balances flexibility and efficiency by storing partially computed action values: predictions about future events. These pre-computation strategies differ in how they update their choices following changes in a task. The successor representation's reliance on stored predictions about future states predicts a unique signature of insensitivity to changes in the task's sequence of events, but flexible adjustment following changes to rewards. We provide evidence for such differential sensitivity in two behavioural studies with humans. These results suggest that the successor representation is a computational substrate for semi-flexible choice in humans, introducing a subtler, more cognitive notion of habit.

An Assessment of the Primary Payer Variable among Breast and Colorectal Cancer Cases in the Massachusetts Cancer Registry, 2005-2009.

The Massachusetts Cancer Registry (MCR) reviewed the medical charts of 5,348 randomly selected breast and colorectal cancer cases diagnosed from 2005 to 2009. The purpose of this study was to assess the reliability of primary payer at diagnosis in the MCR database and to examine primary payer and the first course of treatment of individual cancer patients. For the first period (2005-2006), private insurance (72.6% agreement) and Medicare (84.3% agreement) indicated strong agreement with kappa values of 0.62 and 0.72, respectively. Agreement for the later period was again stronger in the private insurance and Medicare categories (kappa= 0.63 and 0.74, respectively).

Crowd control: sex ratio affects sexually selected cuticular hydrocarbons in male Drosophila serrata.

Although it is advantageous for males to express costly sexually selected signals when females are present, they may also benefit from suppressing these signals to avoid costly interactions with rival males. Cuticular chemical profiles frequently function as insect sexual signals; however, few studies have asked whether males alter these signals in response to their social environment. In Drosophila serrata, an Australian fly, there is sexual selection for a multivariate combination of male cuticular hydrocarbons (CHCs). Here, we show that the ratio of females to males that an adult male experiences has a strong effect on his CHC expression, with female-biased adult sex ratios eliciting greater expression of CHC profiles associated with higher male mating success. Classical models predict that male reproductive investment should be highest when there is a small but nonzero number of rivals, but we found that males expressed the most attractive combination of CHCs when there were no rivals. We found that male CHCs were highly sensitive to adult sex ratio, with males expressing higher values of CHC profiles associated with greater mating success as the ratio of females to males increased. Moreover, sex ratio has a stronger effect on male CHC expression than adult density. Finally, we explore whether sex ratio affects the variance among a group of males in their CHC expression, as might be expected if individuals respond differently to a given social environment, but find little effect. Our results reveal that subtle differences in social environment can induce plasticity in male chemical signal expression.

Female choice for male cuticular hydrocarbon profile in decorated crickets is not based on similarity to their own profile.

Indirect genetic benefits derived from female mate choice comprise additive (good genes) and nonadditive genetic benefits (genetic compatibility). Although good genes can be revealed by condition-dependent display traits, the mechanism by which compatibility alleles are detected is unclear because evaluation of the genetic similarity of a prospective mate requires the female to assess the genotype of the male and compare it to her own. Cuticular hydrocarbons (CHCs), lipids coating the exoskeleton of most insects, influence female mate choice in a number of species and offer a way for females to assess genetic similarity of prospective mates. Here, we determine whether female mate choice in decorated crickets is based on male CHCs and whether it is influenced by females' own CHC profiles. We used multivariate selection analysis to estimate the strength and form of selection acting on male CHCs through female mate choice, and employed different measures of multivariate dissimilarity to determine whether a female's preference for male CHCs is based on similarity to her own CHC profile. Female mating preferences were significantly influenced by CHC profiles of males. Male CHC attractiveness was not, however, contingent on the CHC profile of the choosing female, as certain male CHC phenotypes were equally attractive to most females, evidenced by significant linear and stabilizing selection gradients. These results suggest that additive genetic benefits, rather than nonadditive genetic benefits, accrue to female mate choice, in support of earlier work showing that CHC expression of males, but not females, is condition dependent.

An assessment of the reliability of race, Hispanic ethnicity, birthplace, and tobacco history data in the Massachusetts cancer registry, 2005-2009.

The Massachusetts Cancer Registry (MCR) reviewed the medical charts of 5,438 randomly selected breast and colorectal cancer cases diagnosed from 2005-2009 in part to assess the reliability of the race, Hispanic ethnicity, birth country, and tobacco history variables. The kappa statistic was used to assess the reliability between the originally reported variable and the reabstracted variable. There was strong agreement of kappa score for race among whites, blacks, and other (Asian, Native American), indicating a good quality of race data. The agreement for birth country was strongest among those not born in the United States with a statistically significantly higher kappa score compared to the other categories. Agreement for Hispanic ethnicity was strongest for non-Hispanics, Puerto Ricans, Central Americans, and Dominicans, groups that represent the majority of Hispanics in Massachusetts. The agreement for tobacco history was strongest among current tobacco users. This study provided useful information on the reliability of the race, Hispanic ethnicity, and birthplace variables, which are frequently used in MCR reports. It also provided heretofore unknown data on the reliability of the tobacco history variable. All categories of the race variable were very reliable as were the categories of Puerto Rican, Dominican, and Central American. Hispanic, NOS was not as reliable due to the large Portuguese population with Hispanic sounding surnames. Birth country was not as reliable due to the paucity of the data in many of the larger facilities in the state.

Sexual selection on Drosophila serrata male pheromones does not vary with female age or mating status.

Mate preferences are costly and are thought to evolve due to the direct and/or indirect benefits they provide. Such costs and benefits may vary in response to intrinsic and extrinsic factors with important evolutionary consequences. Limited attention has been given to quantifying such variation and understanding its causes, most notably with respect to the direction and strength of preferences for multivariate sexual displays. In Drosophila serrata, female preferences target a pheromone blend of long-chain cuticular hydrocarbons (CHCs). We used a factorial design to test whether female age and mating status generated variation in the strength and direction of sexual selection on male CHCs. Replicate choice mating trials were conducted using young and old females (4 or 10 days post-emergence) that were either virgin or previously mated. The outcome of such trials is known to capture variation in female mate preferences, although male-male interactions may also contribute. Directional sexual selection on male CHCs was highly significant within each treatment, but there was little evidence of any variation among treatments. The absence of treatment effects implies that the multivariate combination of male CHCs preferred by females was constant with respect to female age and mating status. To the extent that male-male interactions may also contribute, our results similarly imply that these did not vary among treatments groups. With respect to D. serrata mate preferences, our results suggest that either plasticity with respect to age and mating status is not beneficial to females, or preference expression is somehow constrained.

Multitasking versus multiplexing: Toward a normative account of limitations in the simultaneous execution of control-demanding behaviors.

Why is it that behaviors that rely on control, so striking in their diversity and flexibility, are also subject to such striking limitations? Typically, people cannot engage in more than a few-and usually only a single-control-demanding task at a time. This limitation was a defining element in the earliest conceptualizations of controlled processing; it remains one of the most widely accepted axioms of cognitive psychology, and is even the basis for some laws (e.g., against the use of mobile devices while driving). Remarkably, however, the source of this limitation is still not understood. Here, we examine one potential source of this limitation, in terms of a trade-off between the flexibility and efficiency of representation ("multiplexing") and the simultaneous engagement of different processing pathways ("multitasking"). We show that even a modest amount of multiplexing rapidly introduces cross-talk among processing pathways, thereby constraining the number that can be productively engaged at once. We propose that, given the large number of advantages of efficient coding, the human brain has favored this over the capacity for multitasking of control-demanding processes.

Food fight: sexual conflict over free amino acids in the nuptial gifts of male decorated crickets.

In decorated crickets, Gryllodes sigillatus, the spermatophore that a male transfers at mating includes a gelatinous spermatophylax that the female consumes, delaying her removal of the sperm-filled ampulla. Male fertilization success increases with the length of time females spend feeding on the spermatophylax, while females may benefit by prematurely discarding the spermatophylaxes of undesirable males. This sexual conflict should favour males that produce increasingly appealing spermatophylaxes, and females that resist this manipulation. To determine the genetic basis of female spermatophylax feeding behaviour, we fed spermatophylaxes to females of nine inbred lines and found that female genotype had a major influence on spermatophylax feeding duration. The amino acid composition of the spermatophylax was also significantly heritable. There was a positive genetic correlation between spermatophylax feeding duration and the gustatory appeal of the spermatophylax. This correlation suggests that genes expressed in males that produce more manipulative spermatophylaxes are positively linked to genes expressed in females that make them more vulnerable to manipulation. Outbred females spent less time feeding on spermatophylaxes than inbred females, and thus showed greater resistance to male manipulation. Further, in a nonspermatophylax producing cricket (Acheta domesticus), females were significantly more prone to feeding on spermatophylaxes than outbred female Gryllodes. Collectively, these results suggest a history of sexually antagonistic coevolution over the consumption of nuptial food gifts.

Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers.

PURPOSE: The objective of this study was to estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers; and measure the extent to which host, family history, and cancer treatment-related factors modify the risk. PATIENTS AND METHODS: Patients were 810 women, with stage I or II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up. RESULTS: Overall, 149 subjects (18.4%) developed a contralateral breast cancer. The 15-year actuarial risk of contralateral breast cancer was 36.1% for women with a BRCA1 mutation and was 28.5% for women with a BRCA2 mutation. Women younger than 50 years of age at the time of breast cancer diagnosis were significantly more likely to develop a contralateral breast cancer at 15 years, compared with those older than 50 years (37.6 vs 16.8%; P=0.003). Women aged <50 years with two or more first-degree relatives with early-onset breast cancer were at high risk of contralateral breast cancer, compared with women with fewer, or no first-degree relatives with breast cancer (50 vs 36%; P=0.005). The risk of contralateral breast cancer was reduced with oophorectomy (RR 0.47; 95% CI 0.30-0.76; P=0.002). CONCLUSION: The risk of contralateral breast cancer risk in BRCA mutation carriers declines with the age of diagnosis and increases with the number of first-degree relatives affected with breast cancer. Oophorectomy reduces the risk of contralateral breast cancer in young women with a BRCA mutation.

Give 'til it hurts: trade-offs between immunity and male reproductive effort in the decorated cricket, Gryllodes sigillatus.

Trade-offs between life-history variables can be manifested at either the phenotypic or genetic level, with vastly different evolutionary consequences. Here, we examined whether male decorated crickets (Gryllodes sigillatus) from eight inbred lines and the outbred founder population from which they were derived, trade-off immune effort [lytic activity, phenoloxidase (PO) activity or encapsulation] to produce spermatophylaxes: costly nuptial food gifts essential for successful sperm transfer. Canonical correlation analysis of the outbred population revealed a trade-off between spermatophylax mass and lytic activity. Analysis of our inbred lines, however, revealed that although PO activity, encapsulation, body mass, spermatophylax mass and ampulla (sperm capsule) mass were all highly heritable, lytic activity was not, and there was, therefore, no negative genetic correlation between lytic activity and spermatophylax mass. Thus, males showed a phenotypic but not a genetic trade-off between spermatophylax mass and lytic activity, suggesting that this trade-off is mediated largely by environmental factors.

Inbred decorated crickets exhibit higher measures of macroparasitic immunity than outbred individuals.

Inbreeding is assumed to have negative effects on fitness, including the reduced ability to withstand immune challenges. We examined the immunological consequences of inbreeding in decorated crickets, Gryllodes sigillatus, by comparing lytic activity, phenoloxidase (PO) activity, and encapsulation ability of crickets from eight inbred lines with that of crickets from the outbred founder population. Surprisingly, crickets from inbred lines had a greater encapsulation ability compared with crickets from the outbred population. We suggest that because inbred crickets have reduced reproductive effort, they may, therefore, have the option of devoting more resources to this form of immunity than outbred individuals. We also found that both inbred and outbred females had higher immunity than males in PO activity and implant darkness. This result supports the hypothesis that females should devote more effort to somatic maintenance and immunity than males. PO activity and implant darkness were heritable in both males and females, but lytic activity was only heritable in females. Males and females differed in the heritability of, and genetic correlations among, immune traits, suggesting that differences in selective pressures on males and females may have resulted in a sexual conflict over optimal immune trait values.

Lovesick: immunological costs of mating to male sagebrush crickets.

A growing body of evidence suggests that resources invested in reproduction often come at the expense of the ability to mount an immune response. During mating, female sagebrush crickets, Cyphoderris strepitans, consume the ends of the male's hind wings and ingest his haemolymph. Previous research has shown that this behaviour impairs the ability of males to secure additional matings. One hypothesis to account for this effect is that wing wounding triggers an energetically costly immune response, such that nonvirgin males are unable to sustain the costly acoustical signalling needed to attract additional females. To test this hypothesis, we injected virgin males with lipopolysaccharides (LPS) to provoke an immune response, and monitored their mating success in the field. LPS-injected virgin males took significantly longer to mate than sham-injected virgin males, and spent significantly less time calling. We also compared virgin, nonvirgin and experimentally wing-wounded virgin males with respect to: (1) their ability to encapsulate a foreign invader via the accumulation of haemocytes and deposition of melanin and (2) baseline levels of phenoloxidase (PO), a key enzyme in the biochemical cascade leading to the production of melanin. Although encapsulation ability did not differ with reproductive experience, virgin males had significantly higher levels of PO than either nonvirgin or experimentally wing-wounded virgin males. These results suggest that wing-wounding alone is sufficient to impair male immunity, and that males trade-off investment in reproduction and immunity.

Development and testing of a decision aid for breast cancer prevention for women with a BRCA1 or BRCA2 mutation.

For women who carry a mutation in BRCA1 or BRCA2, the risk of breast cancer is up to 87% by the age of 70. There are options available to reduce the risk of breast cancer; however, each option has both risks and benefits, which makes decision making difficult. The objective is to develop and pilot test a decision aid for breast cancer prevention for women with a BRCA1 or BRCA2 mutation. The decision aid was developed and evaluated in three stages. In the first stage, the decision aid was developed and reviewed by cancer genetics experts. The second stage was a review of the decision aid by women with a BRCA1 or BRCA2 mutation for acceptability and feasibility. The final stage was a pre-test--post-test evaluation of the decision aid. Twenty-one women completed the pre-test questionnaire and 20 completed the post-test questionnaire. After using the decision aid, there was a significant decline in mean decisional conflict scores (p = 0.001), a significant improvement in knowledge scores (p = 0.004), and fewer women uncertain about prophylactic mastectomy (p = 0.003) and prophylactic oophorectomy (p = 0.009). Use of the decision aid decreased decisional conflict to levels suggestive of implementation of a decision. In addition, knowledge levels increased and choice predisposition changed with fewer women being uncertain about each option. This has significant clinical implications as it implies that with greater uptake of cancer prevention options by women with a BRCA1 or BRCA2 mutation, fewer women will develop and/or die of hereditary breast cancer.

Geographic assessment of breast cancer screening by towns, zip codes, and census tracts.

Early detection is the primary way to control breast cancer, and mammography screening can reduce breast cancer mortality 30 to 40 percent among women aged 50 years and older. Geographic areas with a high proportion of cases with late-stage diagnoses may reflect gaps in screening efforts. We used a spatial scan statistic, adjusting for the multitude of possible region locations and sizes, to test whether any particular region of Massachusetts had statistically significant excesses of late-stage diagnoses during the period 1982 to 1986. The novel geographic analysis technique utilized here can also be used in the control of other types of cancer.

Primary brain tumor incidence rates in four United States regions, 1985-1989: a pilot study.

There has been controversy in the last decade over whether the reported increase in brain tumors reflects a real increase in incidence rates. Incidence data on the full spectrum of brain tumors is lacking in the discussion since current cancer reports in the United States are restricted to malignant tumors. Data on tumors from four population-based cancer registries in the United States were compiled to provide incidence rates of benign and malignant brain tumors and to assess the feasibility of providing these data on a larger scale. A total of 8,070 primary tumors diagnosed from 1985 to 1989 in Connecticut, Massachusetts, Missouri and Utah were obtained. Brain tumors were defined using the International Classification of Diseases for Oncology codes 191.0-191.9, 192.0-192.3, 192.8-192.9 and 194.3-194.4. Stratum-specific incidence rates by location and histology were estimated by sex, age and region. Age-adjusted rates were standardized to the 1970 United States population. An age-adjusted incidence rate of 9.4/10(5) was observed, which reflects a 36% increase in males and a 68% increase in females over the rate based on malignant tumors alone from the Surveillance, Epidemiology and End Results cancer reporting system. Incorporating benign tumors into cancer registry data would increase the reported incidence rates primarily in females and for meningiomas and nerve sheath tumors. This expanded incidence rate represents a substantial improvement in the ability to describe the occurrence of these complex tumors by subtype with a modest increase in overall case registrations for cancer registries. Centralization of data on all brain tumors appears feasible. Variations in histology-specific rates across regions raises questions that need to be addressed about the ascertainment and accuracy of tumor classification. Use of the cancer registration system to improve the reporting of brain tumors in the United States is important to our understanding of the occurrence of these complex tumors and to our ability to conduct large-scale epidemiologic investigations.

A case-control study of testicular cancer using Connecticut tumour registry data.

This case-control study was designed to determine whether males who were exposed to diethylstilboestrol (DES) in utero are at increased risk of testicular cancer. Questionnaires were completed for 79 residents of Connecticut, who were diagnosed with primary cancer of the testes between 1945 and approximately six months into 1980. An equal number of matched controls drawn from birth certificate records available from the Connecticut State Department of Health Services also submitted questionnaires. Information included data on past medical conditions of subjects and obstetrical history of mothers. The major finding of this study was a statistically significant elevated risk for premature birth for the testicular cancer cases. The study failed to show that DES increased the risk for testicular cancer. However, in view of the findings from previous human and animal studies of such abnormalities as undescended and hypoplastic testes as well as the consideration that only the earliest exposed birth cohort has reached the age of substantial cancer risk, it would seem prudent for any male who has been prenatally exposed to DES to seek medical follow-up.

A literature review of midtarsal joint function.

This article focuses on nearly 50 years of research by various authors documenting function and motion of the midtarsal joint. Subtalar joint control of the midtarsal joint, axes of motion, and quantification of range of motion are examined. The evolution of the joint from primates to man and the associated changes in functional requirements are considered.