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Should policymaking assume humans are irrational? Using empirical, theoretical, and philosophical arguments, we suggest a more useful frame is that human behavior is reasonable. Through identifying goals and systemic factors shaping behavior, we suggest that assuming people are reasonable enables behavioral science to be more effective in shaping public policy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Research suggests that people's experiences of COVID-19 lockdowns have been detrimental to their lives and wellbeing. The current research compared the experiences and perceptions on health, wellbeing and social interaction of 300 UK adults and 450 adults in California. Individuals reported whether aspects of their life had changed for the better, worse, or not at all during lockdown in April 2020, and what the "best" and "worst" things about lockdown were. There were more similarities than differences in the regional comparison of perceptions of changes in specific aspects of 'health and wellbeing' and 'social interaction'. Both regions reported the same number and nature of best and worst things about lockdown. Overarching themes of 'health, self and wellbeing', 'being with others', and 'concerns with daily living' were identified. Although reports of life changes and the positives and negatives of lockdown were similar across different demographic groups, some differences were present by age, sex, relationship, and family-status. Incorporating knowledge of unified and positive experiences of lockdown can be useful in informing future lockdown restrictions and supporting the population when restrictions are lifted., Competing Interests: The authors have declared that no competing interests exist in regard to the research. The lead author is a senior editor with Europe’s Journal of Psychology and declared this prior to the review process beginning.

When deciding where to invest, individuals choose mutual funds based on recent past performance, despite standard mandated disclaimers that "past performance does not guarantee future results." Investors would receive better long-term returns by choosing funds with lower fees. We explored the impact of fees and past performance on realistic mutual fund selections across three preregistered repeated-choice experiments ( N = 1,600), while manipulating the presence of disclaimers between participants. Participants persistently chased past performance despite the opportunity to learn about the futility of this strategy during 60 repeated decisions with feedback. The standard regulatory-mandated disclaimer did not help most participants, compared to giving no advice at all, and was even counter-productive for participants with low levels of financial literacy. An alternative disclaimer that explicitly highlighted the advantages of fee minimization reliably helped participants. We show how individuals who lack both financial literacy and prior investment experience are the most susceptible to making poor mutual fund choices and can benefit the most from behavioral interventions such as the new disclaimer tested here. We discuss how these results generalize into real-world investment decisions, and how to design more efficient disclaimers that can be used beyond investment choices. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Genomics data are currently being produced at unprecedented rates, resulting in increased knowledge discovery and submission to public data repositories. Despite these advances, genomic information on African-ancestry populations remains significantly low compared with European- and Asian-ancestry populations. This information is typically segmented across several different biomedical data repositories, which often lack sufficient fine-grained structure and annotation to account for the diversity of African populations, leading to many challenges related to the retrieval, representation and findability of such information. To overcome these challenges, we developed the African Genomic Medicine Portal (AGMP), a database that contains metadata on genomic medicine studies conducted on African-ancestry populations. The metadata is curated from two public databases related to genomic medicine, PharmGKB and DisGeNET. The metadata retrieved from these source databases were limited to genomic variants that were associated with disease aetiology or treatment in the context of African-ancestry populations. Over 2000 variants relevant to populations of African ancestry were retrieved. Subsequently, domain experts curated and annotated additional information associated with the studies that reported the variants, including geographical origin, ethnolinguistic group, level of association significance and other relevant study information, such as study design and sample size, where available. The AGMP functions as a dedicated resource through which to access African-specific information on genomics as applied to health research, through querying variants, genes, diseases and drugs. The portal and its corresponding technical documentation, implementation code and content are publicly available.

Previous research has demonstrated a 'seductive allure' of technical or reductive language such that bad (e.g., circular) explanations are judged better when irrelevant technical terms are included. We aimed to explore if such an effect was observable in relation to a covid-19 vaccinations and if this subsequently affected behavioural intentions to take up a covid-19 vaccine. Using a between subjects design we presented participants (N = 996) with one of four possible types of vignette that explained how covid-19 vaccination and herd immunity works. The explanations varied along two factors: (1) Quality, explanations were either good or bad (i.e., tautological); (2) Language, explanations either contained unnecessary technical language or did not. We measured participants' evaluation of the explanations and intentions to vaccinate. We demonstrate a 'seductive allure' effect of technical language on bad vaccine explanations. However, an opposite 'repellent disdain' effect occurred for good explanations which were rated worse when they contained technical language. Moreover, we show that evaluations of explanations influence intentions to vaccinate. We suggest that misinformation that includes technical language could be more detrimental to vaccination rates. Importantly, however, clear explanatory public health information that omits technical language will be more effective in increasing intentions to vaccinate., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The COVID-19 pandemic constitutes a novel threat and traditional and new media provide people with an abundance of information and misinformation on the topic. In the current study, we investigated who tends to trust what type of mis/information. The data were collected in Norway from a sample of 405 participants during the first wave of COVID-19 in April 2020. We focused on three kinds of belief: the belief that the threat is overrated (COVID-threat skepticism), the belief that the threat is underrated (COVID-threat belief) and belief in misinformation about COVID-19. We studied sociodemographic factors associated with these beliefs and the interplay between attitudes to COVID-19, media consumption and prevention behavior. All three types of belief were associated with distrust in information about COVID-19 provided by traditional media and distrust in the authorities' approach to the pandemic. COVID-threat skepticism was associated with male gender, reduced news consumption since the start of the pandemic and lower levels of precautionary measures. Belief that the COVID-19 threat is underrated was associated with younger age, left-wing political orientation, increased news consumption during the pandemic and increased precautionary behavior. Consistent with the assumptions of the theory of planned behavior, individual beliefs about the seriousness of the COVID-19 threat predicted the extent to which individual participants adopted precautionary health measures. Both COVID-threat skepticism and COVID-threat belief were associated with endorsement of misinformation on COVID-19. Participants who endorsed misinformation tended to: have lower levels of education; be male; show decreased news consumption; have high Internet use and high trust in information provided by social media. Additionally, they tended to endorse multiple misinformation stories simultaneously, even when they were mutually contradictory. The strongest predictor for low compliance with precautionary measures was endorsement of a belief that the COVID-19 threat is overrated which at the time of the data collection was held also by some experts and featured in traditional media. The findings stress the importance of consistency of communication in situations of a public health threat., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Filkuková, Ayton, Rand and Langguth.)

The attempts to mitigate the unprecedented health, economic, and social disruptions caused by the COVID-19 pandemic are largely dependent on establishing compliance to behavioral guidelines and rules that reduce the risk of infection. Here, by conducting an online survey that tested participants' knowledge about the disease and measured demographic, attitudinal, and cognitive variables, we identify predictors of self-reported social distancing and hygiene behavior. To investigate the cognitive processes underlying health-prevention behavior in the pandemic, we co-opted the dual-process model of thinking to measure participants' propensities for automatic and intuitive thinking vs. controlled and reflective thinking. Self-reports of 17 precautionary behaviors, including regular hand washing, social distancing, and wearing a face mask, served as a dependent measure. The results of hierarchical regressions showed that age, risk-taking propensity, and concern about the pandemic predicted adoption of precautionary behavior. Variance in cognitive processes also predicted precautionary behavior: participants with higher scores for controlled thinking (measured with the Cognitive Reflection Test) reported less adherence to specific guidelines, as did respondents with a poor understanding of the infection and transmission mechanism of the COVID-19 virus. The predictive power of this model was comparable to an approach (Theory of Planned Behavior) based on attitudes to health behavior. Given these results, we propose the inclusion of measures of cognitive reflection and mental model variables in predictive models of compliance, and future studies of precautionary behavior to establish how cognitive variables are linked with people's information processing and social norms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Thoma, Weiss-Cohen, Filkuková and Ayton.)

Background: By the end of March 2020, more than a fifth of the world's population was in various degrees of "lockdown" in order to slow the spread of COVID-19. This enforced confinement led some to liken lockdown to imprisonment. We directly compared individual's experiences of lockdown with prisoners' experiences of imprisonment in order to determine whether psychological parallels can be drawn between these two forms of confinement., Methods: Online surveys of adults in lockdown in the UK ( N = 300) and California ( N = 450) were conducted 4 and 5 weeks into lockdown in each region, respectively. The UK data was then compared to Souza and Dhami's (2010) sample of 267 medium security prisoners in England, and the Californian data was compared to Dhami et al.'s (2007) sample of 307 medium security Federal prisoners in California. We measured the effects of Group (Lockdown v. Prison) on five categories of dependent variables (i.e., activity, social contact, thoughts, feelings, and rule-breaking), controlling for demographic differences between the groups., Results: In both regions, people in lockdown thought significantly less often about missing their freedom, as well as missing their family and friends living elsewhere than did first-time prisoners. However, people in lockdown in both regions were also significantly less engaged in a range of daily activities than were first-time prisoners. Additionally, in both regions, people in lockdown reported feeling more hopeless than first-time prisoners., Conclusion: Although Governments introducing lockdown policies do not intend to punish their citizens as courts do when sending convicted offenders to prison, such policies can have unintended adverse consequences. Psychological parallels can be drawn between the two forms of confinement., (Copyright © 2020 Dhami, Weiss-Cohen and Ayton.)

Financial risky decisions and evaluations pervade many human everyday activities. Scientific research in such decision-making typically explores the influence of socio-economic and cognitive factors on financial behavior. However, very little research has explored the holistic influence of contextual, emotional, and hormonal factors on preferences for risk in insurance and investment behaviors. Accordingly, the goal of this review article is to address the complexity of individual risky behavior and its underlying psychological factors, as well as to critically examine current regulations on financial behavior.

Retrospective evaluation (RE) of event sequences is known to be biased in various ways. The present paper presents a series of studies that examined the suggestion that the moments that are the most accessible in memory at the point of RE contribute to these biases. As predicted by this memory-based analysis, Experiment 1 showed that pleasantness ratings of word lists were biased by the presentation position of a negative item and by how easy the negative information was to retrieve. Experiment 2 ruled out the hypothesis that these findings were due to the dual nature of the task called upon. Experiment 3 further manipulated the memorability of the negative items--and corresponding changes in RE were as predicted. Finally, Experiment 4 extended the findings to more complex stimuli involving event narratives. Overall, the results suggest that assessments were adjusted based on the retrieval of the most readily available information.

Background: Computer aids can affect decisions in complex ways, potentially even making them worse; common assessment methods may miss these effects. We developed a method for estimating the quality of decisions, as well as how computer aids affect it, and applied it to computer-aided detection (CAD) of cancer, reanalyzing data from a published study where 50 professionals ("readers") interpreted 180 mammograms, both with and without computer support., Method: We used stepwise regression to estimate how CAD affected the probability of a reader making a correct screening decision on a patient with cancer (sensitivity), thereby taking into account the effects of the difficulty of the cancer (proportion of readers who missed it) and the reader's discriminating ability (Youden's determinant). Using regression estimates, we obtained thresholds for classifying a posteriori the cases (by difficulty) and the readers (by discriminating ability)., Results: Use of CAD was associated with a 0.016 increase in sensitivity (95% confidence interval [CI], 0.003-0.028) for the 44 least discriminating radiologists for 45 relatively easy, mostly CAD-detected cancers. However, for the 6 most discriminating radiologists, with CAD, sensitivity decreased by 0.145 (95% CI, 0.034-0.257) for the 15 relatively difficult cancers., Conclusions: Our exploratory analysis method reveals unexpected effects. It indicates that, despite the original study detecting no significant average effect, CAD helped the less discriminating readers but hindered the more discriminating readers. Such differential effects, although subtle, may be clinically significant and important for improving both computer algorithms and protocols for their use. They should be assessed when evaluating CAD and similar warning systems.

Six experiments studied relative frequency judgment and recall of sequentially presented items drawn from 2 distinct categories (i.e., city and animal). The experiments show that judged frequencies of categories of sequentially encountered stimuli are affected by certain properties of the sequence configuration. We found (a) a first-run effect whereby people overestimated the frequency of a given category when that category was the first repeated category to occur in the sequence and (b) a dissociation between judgments and recall; respondents may judge 1 event more likely than the other and yet recall more instances of the latter. Specifically, the distribution of recalled items does not correspond to the frequency estimates for the event categories, indicating that participants do not make frequency judgments by sampling their memory for individual items as implied by other accounts such as the availability heuristic (Tversky & Kahneman, 1973) and the availability process model (Hastie & Park, 1986). We interpret these findings as reflecting the operation of a judgment heuristic sensitive to sequential patterns and offer an account for the relationship between memory and judged frequencies of sequentially encountered stimuli.

Background: Our aim was to determine whether anaesthetists routinely confirm their ability to ventilate a patient's lungs by a facemask before the administration of a neuromuscular blocker and the rationale for this practice., Methods: An online survey of trainee and non-trainee anaesthetists working in hospitals forming part of the Central London School of Anaesthesia collected 136 complete data sets over a 3 month period., Results: Seventy-eight of 136 (57%) routinely checked they could ventilate by the facemask ('checkers'). The reasons given for this varied, though the most common was the ability to 'enable escape wake-up'. The practice was most commonly adopted by anaesthetists with less experience. In a hypothetical 'cannot ventilate' scenario, the use of succinylcholine was advocated by the majority of respondents, both 'checkers' and 'non-checkers'., Conclusions: Despite the lack of firm evidence to support the practice of confirming the ability to ventilate the lungs before administering a neuromuscular blocking drug (NMB), we found strongly held views that supported the practice and equally strongly held views that opposed it. However, in a hypothetical emergency situation where ventilation by the facemask after induction of anaesthesia was impossible, the majority of respondents (including 'checkers') would administer a neuromuscular blocker. This apparent paradox can be explained by well-recognized psychological mechanisms. We suggest that in checking the ability to ventilate by the facemask, some anaesthetists are seeking information that may be relevant but not instrumental in deciding when to administer an NMB.

A proposed remedy for biased affective forecasts is to base judgments on the actual feelings of people (surrogates) currently experiencing the event, rather than using imagination which conjures an inaccurate vision of the future. Gilbert et al. (2009) forced people to use surrogate reports by withholding all event information, resulting in better predictions. However, in life surrogate information rarely supplants event information--can people effectively integrate both types of information into their judgments? In five studies, respondents predicted the impact of a health state on their own happiness. Respondents incorporated surrogate information into their judgments both in the presence and absence of event information. However, they inappropriately discounted other people's experiences as a valid predictor of their own--particularly in the presence of event information--and imagined their happiness would be different to surrogates' happiness. Excluding preexisting event knowledge, changing the size of the surrogate sample, or increasing the size of the response scale did not alter the adjustment. Although surrogate information improved affective forecasts, its influence was diminished by the presence of event information., (Copyright 2009 APA)

In 5 experiments, we studied precautionary decisions in which participants decided whether or not to buy insurance with specified cost against an undesirable event with specified probability and cost. We compared the risks taken for precautionary decisions with those taken for equivalent monetary gambles. Fitting these data to Tversky and Kahneman's (1992) prospect theory, we found that the weighting function required to model precautionary decisions differed from that required for monetary gambles. This result indicates a failure of the descriptive invariance axiom of expected utility theory. For precautionary decisions, people overweighted small, medium-sized, and moderately large probabilities-they exaggerated risks. This effect is not anticipated by prospect theory or experience-based decision research (Hertwig, Barron, Weber, & Erev, 2004). We found evidence that exaggerated risk is caused by the accessibility of events in memory: The weighting function varies as a function of the accessibility of events. This suggests that people's experiences of events leak into decisions even when risk information is explicitly provided. Our findings highlight a need to investigate how variation in decision content produces variation in preferences for risk.

Any individual's response intended to be random should be as probable as any other. However, 3 experiments show that many people's independent responses depart from the expected chance distribution. Participants responding to instructions of chance and related concepts favor the available options unequally in a similar way. Consequently, in hide-and-seek games, hiders converge on certain locations and are thereby detected beyond chance by seekers who share their preferences. People agree on salient and on nonsalient options, both of which are preferred under different instructions and even in the absence of instructions. Group responses strongly correlate under diverse, even opposing (e.g., competitive and cooperative) directions. Apparently, common default tendencies, combining random and aesthetic choices, are only somewhat modified under specific instructions. Maximal agreement with others is obtained through one's own aesthetic choices. Hence, implementing one's personal aesthetic preferences succeeds in matching others' choices even better than deliberate mutual coordination efforts. These results broadly replicate in 1- and 2-dimensional tasks. Implications of the findings, their possible roots, and their connection to constructs from, e.g., game theory and subjective-complexity research, are discussed., (Copyright 2009 APA, all rights reserved.)

Background: People overestimate the impact of health conditions on happiness, putatively because they focus excessively on resulting negative consequences while disregarding the impact of other unchanged aspects of life on happiness. However, typically, inferences about accuracy have been based on a confound of the viewpoint of judgments(Self/Other) with whether the respondent has the condition (Have/Not-have)--an important issue because people often judge themselves as different to others. This study measured Haves' and Not-haves' judged impact on happiness--for self and other--of several chronic health conditions, and whether "defocusing" respondents improved judgment., Method: 80 Haves and 80 Not-haves predicted the impact of health conditions on their own and others' happiness using a questionnaire, after some participated in a defocusing exercise. Haves also indicated their preferences for their health condition over other conditions., Results: Although Haves made more accurate forecasts than Not-haves, both overestimated the impact of health conditions on others' happiness--yet defocusing respondents prior to prediction had no effect. Haves were aware that Not-haves misjudge Haves' happiness, but underestimated the bias in Not-haves' judgments. Whereas Haves judged they were more happy than other Haves, Not-haves predicted they would be less happy than others if living with a health condition. Finally, Haves' preferences for health conditions exhibited an endowment effect., Conclusion: The existence of an impact bias is not attributable to the confounding of self/other and Have/Not-have in other studies. People who have a condition forecasted others' happiness more accurately, suggesting that experience of one condition helps in comprehending life with another.

Prisoners' forecasts of post-release success may have implications for how they respond to imprisonment, release, and parole decisions. We examined sentenced US and UK prisoners' forecasts of recidivism, and how well UK prisoners believed they would fare compared to the average other prisoner. In both samples, forecasts of recidivism were unrealistically optimistic when compared to official statistics on recidivism. UK prisoners also demonstrated a self-enhancement bias by forecasting that they were less likely to re-offend than other prisoners. Prisoners' forecasts of recidivism were predicted by only a few of the pre-prison, in-prison, and post-prison factors that have been shown to be associated with actual recidivism. We discuss the implications of these findings and propose avenues for future research.

We summarise a set of analyses and studies conducted to assess the effects of the use of a computer-aided detection (CAD) tool in breast screening. We have used an interdisciplinary approach that combines: (a) statistical analyses inspired by reliability modelling in engineering; (b) experimental studies of decisions of mammography experts using the tool, interpreted in the light of human factors psychology; and (c) ethnographic observations of the use of the tool both in trial conditions and in everyday screening practice. Our investigations have shown patterns of human behaviour and effects of computer-based advice that would not have been revealed by a standard clinical trial approach. For example, we found that the negligible measured effect of CAD could be explained by a range of effects on experts' decisions, beneficial in some cases and detrimental in others. There is some evidence of the latter effects being due to the experts using the computer tool differently from the intentions of the developers. We integrate insights from the different pieces of evidence and highlight their implications for the design, evaluation and deployment of this sort of computer tool.

The representativeness heuristic has been invoked to explain two opposing expectations--that random sequences will exhibit positive recency (the hot hand fallacy) and that they will exhibit negative recency (the gambler's fallacy). We propose alternative accounts for these two expectations: (1) The hot hand fallacy arises from the experience of characteristic positive recency in serial fluctuations in human performance. (2) The gambler's fallacy results from the experience of characteristic negative recency in sequences of natural events, akin to sampling without replacement. Experiment 1 demonstrates negative recency in subjects' expectations for random binary outcomes from a roulette game, simultaneously with positive recency in expectations for another statistically identical sequence-the successes and failures of their predictions for the random outcomes. These findings fit our proposal but are problematic for the representativeness account. Experiment 2 demonstrates that sequence recency influences attributions that human performance or chance generated the sequence.

Rationale and Objectives: To investigate the effects of incorrect computer output on the reliability of the decisions of human users. This work followed an independent UK clinical trial that evaluated the impact of computer-aided detection(CAD) in breast screening. The aim was to use data from this trial to feed into probabilistic models (similar to those used in "reliability engineering") which would detect and assess possible ways of improving the human-CAD interaction. Some analyses required extra data; therefore, two supplementary studies were conducted. Study 1 was designed to elucidate the effects of computer failure on human performance. Study 2 was conducted to clarify unexpected findings from Study 1., Materials and Methods: In Study 1, 20 film readers viewed 60 sets of mammograms (30 of which contained cancer) and provided "recall/no recall" decisions for each case. Computer output for each case was available to the participants. The test set was designed to contain an unusually large proportion (50%) of cancers for which CAD had generated incorrect output. In Study 2, 19 different readers viewed the same set of cases in similar conditions except that computer output was not available., Results: The average sensitivity of readers in Study 1 (with CAD) was significantly lower than the average sensitivity of read-ers in Study 2 (without CAD). The difference was most marked for cancers for which CAD failed to provide correct prompting., Conclusion: Possible automation bias effects in CAD use deserve further study because they may degrade human decision-making for some categories of cases under certain conditions. This possibility should be taken into account in the assessment and design of CAD tools.

The MLL (Mixed Lineage Leukemia) gene is a common target for chromosomal translocations associated with human acute leukemias. These translocations result in a gain of MLL function by generating novel chimeric proteins containing the amino-terminus of MLL fused in-frame with one of 30 distinct partner proteins. Structure/function studies using an in vitro myeloid progenitor immortalization assay have revealed that at least four nuclear partner proteins contribute transcriptional effector properties to MLL to produce a range of chimeric transcription factors with leukemogenic potential. Mouse models suggest that expression of an MLL fusion protein is necessary but not sufficient for leukemogenesis. Interestingly, whilst all MLL fusion proteins tested so far phenocopy each other with respect to in vitro immortalization, the latency period required for the onset of acute leukemia in vivo is variable and partner protein dependent. We discuss potential mechanisms that may account for the ability of distinct MLL fusion proteins to promote short or long latency leukemogenesis.

The mixed lineage leukemia gene (MLL) was originally identified through its involvement in reciprocal translocations in leukemias. MLL codes for a large multidomain protein and bears homology to the Drosophila developmental control gene trithorax in two small domains in the amino terminal region, the central zinc finger domain and the carboxy SET domain. Like the Drosophila trx, MLL has also been shown to be a positive regulator of Hox gene expression. We have targeted Mll (the murine homologue of MLL) in exon 5 causing expression of three truncated in-frame Mll transcripts. These transcripts retain all or some of the AT hook motifs and the DMT domain. This mutant allele causes early in vivo preimplantation lethality of homozygous embryos prior to the 2-cell stage. Embryos cultured in vitro progress to the 2-cell stage, but further development is arrested. The heterozygotes exhibit mild skeletal defects as well as defects in some neuroectodermal derivatives.

The t(11;19)(q23;p13.1) chromosomal translocation in acute myeloid leukemias fuses the gene encoding transcriptional elongation factor ELL to the MLL gene with consequent expression of an MLL-ELL chimeric protein. To identify potential mechanisms of leukemogenesis by MLL-ELL, its transcriptional and oncogenic properties were investigated. Fusion with MLL preserves the transcriptional elongation activity of ELL but relocalizes it from a diffuse nuclear distribution to the nuclear bodies characteristic of MLL. Using a serial replating assay, it was demonstrated that the MLL-ELL chimeric protein is capable of immortalizing clonogenic myeloid progenitors in vitro after its retroviral transduction into primary murine hematopoietic cells. However, a structure-function analysis indicates that the elongation domain is not essential for myeloid transformation because mutants lacking elongation activity retain a potent ability to immortalize myeloid progenitors. Rather, the highly conserved carboxyl terminal R4 domain is both a necessary and a sufficient contribution from ELL for the immortalizing activity associated with MLL-ELL. The R4 domain demonstrates potent transcriptional activation properties and is required for transactivation of a HoxA7 promoter by MLL-ELL in a transient transcriptional assay. These data indicate that neoplastic transformation by the MLL-ELL fusion protein is likely to result from aberrant transcriptional activation of MLL target genes. Thus, in spite of the extensive diversity of MLL fusion partners, these data, in conjunction with previous studies of MLL-ENL, suggest that conversion of MLL to a constitutive transcriptional activator may be a general model for its oncogenic conversion in myeloid leukemias. (Blood. 2000;96:3887-3893)

Objectives: The objective was to test whether individuals high in delusional ideation exhibit a reasoning bias on tasks involving hypothesis testing and probability judgments. On the basis of previous findings (e.g. Garety, Hemsley & Wessely, 1991), it was predicted that individuals high in delusional ideation would exhibit a 'jump-to-conclusions' style of reasoning and would be less sensitive to the effects of random variation, in comparison to individuals low in delusional ideation., Design: A non-randomized matched groups design was employed enabling the performance of the delusion prone individuals to be compared to that of a control group., Method: Forty individuals, selected from the normal population, were divided into groups high and low in delusional ideation, according to their scores on the Peters et al. Delusions Inventory (Peters, Day & Garety, 1996), and were compared on two tasks involving probability judgment and two tasks involving hypothesis testing., Results: Although no significant differences were found on tasks involving hypothesis testing and the aggregation of probabilistic information, it was found that individuals high in delusional ideation had a 'jump-to-conclusions' style of data gathering and were less sensitive to the effects of random variation, in comparison to individuals low in delusional ideation., Conclusions: In conclusion, although individuals high in delusional ideation were not found to have a general reasoning bias, some evidence of a more specific bias was found. It is thought that these aberrations may play some role in delusion formation in schizophrenia and paranoia.

Topoisomerase II is a key target for several anti-cancer drugs used for breast cancer therapy, including doxorubicin, epirubicin and mitoxantrone. Two isoforms of topoisomerase II (alpha and beta) have been described in human cells which differ in their subcellular localisation, biochemical properties and susceptibility to inhibition by anti-cancer drugs. The relative level of expression of the alpha and beta isoforms may contribute to the degree of tumour responsiveness to different chemotherapeutic agents. To assess the relationship between expression of topoisomerase II isoforms and established prognostic factors and pathological variables, 56 primary breast tumour samples were studied. The expression of the two topoisomerase II genes was apparently not co-ordinately regulated in these tissue samples. There was no relationship between any of the commonly used pathological variables [tumour size, lymph node status, S-phase fraction (SPF)] and the level of expression of topoisomerase II beta mRNA. However, high topoisomerase II alpha gene expression was significantly associated with a high SPF (sign-rank test; P = 0.01). Moreover, the ratio of mRNA levels for topoisomerase II alpha and beta showed a stronger relationship to SPF (median raito 0.62 for tumours with SPF < 10, and 1.64 for SPF > 10; P = 0.0021, sign-rank test). As expected from previous studies, an SPF > 10 was associated with poor overall survival (P = 0.01). Immunohistochemical analysis revealed that topoisomerase II beta was widely distributed ( > 90% positive tumour cells), but that topoisomerase II alpha expression was less widely expressed, with a pattern of expression similar to that of the proliferation-dependent antigen recognised by Ki67. Because topoisomerase II gene expression showed a log-normal distribution, log-transformed data were used in multivariate analysis of relapse-free survival. This showed that lymph node status and topoisomerase II beta mRNA expression were the only significant survival factors (P = 0.001 and 0.05, respectively, with relative risks of 1.3 and 1.8). These results indicate that topoisomerase II alpha, but not beta, expression is dependent upon cellular proliferation status, but that the more widely expressed topoisomerase II beta protein may play a significant role as a target for anti-tumour therapy.

We have identified and further characterized a Caenorhabditis elegans gene, CEZF, that encodes a protein with substantial homology to the zinc finger and leucine zipper motifs of the human gene products AF10, MLLT6, and BR140. The first part of the zinc finger region of CEZF has strong similarity to the corresponding regions of AF10 (66%) and MLLT6 (64%) at the cDNA level. As this region is structurally different from previously described zinc finger motifs, sequence homology searches were done. Twenty-five other proteins with a similar motif were identified. Because the functional domain of this motif is potentially disrupted in leukemia-associated chromosomal translocations, we propose the name of leukemia-associated protein (LAP) finger. On the basis of these comparisons, the LAP domain consensus sequence is Cys1-Xaa1-2-Cys2-Xaa9-21-Cys3-Xaa2-4 -Cys4-Xaa4-5-His5-Xaa2-Cys6-Xaa12-46 - Cys7-Xaa2-Cys8, where subscripted numbers represent the number of amino acid residues. We review the evidence that this motif binds zinc, is the important DNA-binding domain in this group of regulatory proteins, and may be involved in leukemogenesis.

A novel class of conserved transcription factors has been identified from the molecular cloning of AF10, the gene involved in the t(10;11)(p12;q23) translocation of acute myeloid leukemias. AF10 encodes a 109-kD protein of 1,027 amino acids and contains an N-terminal zinc finger region and a C-terminal leucine zipper. These structures have been found to be conserved in sequence and position in three other proteins, AF17, BR140, and a previously unrecognized Caenorhabditis elegans gene, provisionally named CEZF. The overall structure, level of sequence conservation, and expression pattern suggest that these genes encode a new class of transcription factors, some of which are targets for chromosomal translocation in acute leukemia.

Topoisomerases catalyse the interconversion of topological isomers of DNA and have key roles in nucleic acid metabolism. Human cells express two distinct type II topoisomerase isozymes, designated topoisomerase II alpha (170 kDa form) and topoisomerase II beta (180 kDa form). We have isolated cDNA clones encoding the beta isozyme from a human B-cell library. The proposed coding region for the topoisomerase II beta protein is 4,863 nucleotides long and would encode a polypeptide with a calculated M(r) of 182,705. The predicted topoisomerase II beta protein sequence shows striking similarity (72% identical residues) to that of the human alpha isozyme, and homology to topoisomerase II proteins from Drosophila, yeast and bacteria. Regions of greatest amino acid sequence divergence lie at the extreme N-terminus and over a C-terminal domain comprising approximately 25% of the total protein. We have quantified the level of topoisomerase II beta mRNA in a panel of human tumour cell lines of different origin using an RNase protection assay, and compared the level to that of topoisomerase II alpha mRNA. Topoisomerase II beta mRNA was expressed in haemopoietic, epithelial and fibroblast cell lines, although to different extents, with U937 cells (promonocytic leukaemia) showing a particularly high level. There was no obvious relationship in terms of level of expression between the topoisomerase II alpha and beta genes. We have localised the gene encoding topoisomerase II beta protein to chromosome 3p24 in the human genome.