Representing uncertainty in the Rescorla-Wagner model: Blocking, the redundancy effect, and outcome base rate

It is generally assumed that the Rescorla and Wagner (1972) model adequately accommodates the full results of simple cue competition experiments in humans (e.g. Dickinson et al., 1984), while the Bush and Mosteller (1951) model cannot. We present simulations that demonstrate this assumption is wrong in at least some circumstances. The Rescorla-Wagner model, as usually applied, fits the full results of a simple forward cue-competition experiment no better than the Bush-Mosteller model. Additionally, we present a novel finding, where letting the associative strength of all cues start at an intermediate value (rather than zero), allows this modified model to provide a better account of the experimental data than the (equivalently modified) Bush-Mosteller model. This modification also allows the Rescorla-Wagner model to account for a redundancy effect experiment (Uengoer et al., 2013); something that the unmodified model is not able to do. Furthermore, the modified Rescorla-Wagner model can accommodate the effect of varying the proportion of trials on which the outcome occurs (i.e. the base rate) on the redundancy effect (Jones et al., 2019). Interestingly, the initial associative strength of cues varies in line with the outcome base rate. We propose that this modification provides a simple way of mathematically representing uncertainty about the causal status of novel cues within the confines of the Rescorla-Wagner model. The theoretical implications of this modification are discussed. We also briefly introduce free and open resources to support formal modelling in associative learning. Keywords: associative learning, prediction error, uncertainty, modelling, blocking, redundancy effect, open science.</jats:p

Estimating the Prevalence of Sexual Function Problems: The Impact of Morbidity Criteria

Establishing the clinical significance of symptoms of sexual dysfunction is challenging. To address this, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) introduced two new morbidity criteria (duration and symptom severity) to the existing criteria of distress. This study sought to establish the impact of these three criteria on the population prevalence of sexual function problems. The data come from a national probability survey (Natsal-3) and are based on 11,509 male and female participants aged 16-74, reporting at least one sexual partner in the past year. The key outcomes were: proportion of individuals reporting proxy measures of DSM-5 problems, and the proportion of those meeting morbidity criteria. We found that among sexually active men, the prevalence of reporting one or more of four specific sexual problems was 38.2%, but 4.2% after applying the three morbidity criteria; corresponding figures for women reporting one or more of three specific sexual problems, were 22.8% and 3.6%. Just over a third of men and women reporting a problem meeting all three morbidity criteria had sought help in the last year. We conclude that the DSM-5 morbidity criteria impose a focus on clinically significant symptoms

Risk factors for delayed presentation and referral of symptomatic cancer: Evidence for common cancers

Background:It has been suggested that the known poorer survival from cancer in the United Kingdom, compared with other European countries, can be attributed to more advanced cancer stage at presentation. There is, therefore, a need to understand the diagnostic process, and to ascertain the risk factors for increased time to presentation.Methods:We report the results from two worldwide systematic reviews of the literature on patient-mediated and practitioner-mediated delays, identifying the factors that may influence these.Results:Across cancer sites, non-recognition of symptom seriousness is the main patient-mediated factor resulting in increased time to presentation. There is strong evidence of an association between older age and patient delay for breast cancer, between lower socio-economic status and delay for upper gastrointestinal and urological cancers and between lower education level and delay for breast and colorectal cancers. Fear of cancer is a contributor to delayed presentation, while sanctioning of help seeking by others can be a powerful mediator of reduced time to presentation. For practitioner delay, ‘misdiagnosis’ occurring either through treating patients symptomatically or relating symptoms to a health problem other than cancer, was an important theme across cancer sites. For some cancers, this could also be linked to inadequate patient examination, use of inappropriate tests or failing to follow-up negative or inconclusive test results.Conclusion:Having sought help for potential cancer symptoms, it is therefore important that practitioners recognise these symptoms, and examine, investigate and refer appropriately. © 2009 Cancer Research UK All rights reserved

Mild cognitive impairment: the Manchester consensus

Given considerable variation in diagnostic and therapeutic practice, there is a need for national guidance on the use of neuroimaging, fluid biomarkers, cognitive testing, follow-up and diagnostic terminology in mild cognitive impairment (MCI). MCI is a heterogenous clinical syndrome reflecting a change in cognitive function and deficits on neuropsychological testing but relatively intact activities of daily living. MCI is a risk state for further cognitive and functional decline with 5–15% of people developing dementia per year. However, ~50% remain stable at 5 years and in a minority, symptoms resolve over time. There is considerable debate about whether MCI is a useful clinical diagnosis, or whether the use of the term prevents proper inquiry (by history, examination and investigations) into underlying causes of cognitive symptoms, which can include prodromal neurodegenerative disease, other physical or psychiatric illness, or combinations thereof. Cognitive testing, neuroimaging and fluid biomarkers can improve the sensitivity and specificity of aetiological diagnosis, with growing evidence that these may also help guide prognosis. Diagnostic criteria allow for a diagnosis of Alzheimer’s disease to be made where MCI is accompanied by appropriate biomarker changes, but in practice, such biomarkers are not available in routine clinical practice in the UK. This would change if disease-modifying therapies became available and required a definitive diagnosis but would present major challenges to the National Health Service and similar health systems. Significantly increased investment would be required in training, infrastructure and provision of fluid biomarkers and neuroimaging. Statistical techniques combining markers may provide greater sensitivity and specificity than any single disease marker but their practical usefulness will depend on large-scale studies to ensure ecological validity and that multiple measures, e.g. both cognitive tests and biomarkers, are widely available for clinical use. To perform such large studies, we must increase research participation amongst those with MCI

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

Communication between secondary and primary care following self-harm: are National Institute of Clinical Excellence (NICE) guidelines being met?

<p>Abstract</p> <p>Background</p> <p>Most patients contact their general practitioner (GP) following presentation to an Emergency Department (ED) after a self-harm incident, and strategies to help GPs manage these patients include efficient communication between services. The aim of this study was to assess the standard of documentation and communication to primary care from secondary care as recommended by the National Institute of Clinical Excellence (NICE) guidelines on the short-term management of people who self-harm.</p> <p>Methods</p> <p>An audit of medical records (ED and Psychiatric) on people aged 16 years and over who had presented to the ED following self-harm, benchmarked according to government guidelines, was performed. Data were collected over a 4-week period at a general teaching hospital.</p> <p>Results</p> <p>We collected data on 93 consecutive episodes of self-harm; 62% of episodes were communicated to primary care, 58% of these communications were within 24 h and most within 3 days. Patient identifying details and follow-up arrangements were specified in most cases. Communication via psychiatric staff was most detailed. ED clinicians provided few communications and were of limited content. Communication with the patient's GP was not made in half of those cases seen by a mental health specialist.</p> <p>Conclusion</p> <p>Government guidelines are only partially being met. Reliance on communication by ED staff would leave a substantial proportion of patients discharged from the ED with no or minimal communication to primary care. Psychiatric services need to improve the rate of communication to the patient's GP following assessment A national sample of National Health Service (NHS) trusts would establish if this is a problem elsewhere.</p

Getting “Just Deserts” or Seeing the “Silver Lining”: The Relation between Judgments of Immanent and Ultimate Justice

People can perceive misfortunes as caused by previous bad deeds (immanent justice reasoning) or resulting in ultimate compensation (ultimate justice reasoning). Across two studies, we investigated the relation between these types of justice reasoning and identified the processes (perceptions of deservingness) that underlie them for both others (Study 1) and the self (Study 2). Study 1 demonstrated that observers engaged in more ultimate (vs. immanent) justice reasoning for a "good" victim and greater immanent (vs. ultimate) justice reasoning for a "bad" victim. In Study 2, participants' construals of their bad breaks varied as a function of their self-worth, with greater ultimate (immanent) justice reasoning for participants with higher (lower) self-esteem. Across both studies, perceived deservingness of bad breaks or perceived deservingness of ultimate compensation mediated immanent and ultimate justice reasoning respectively. © 2014 Harvey and Callan

Systematic review of factors influencing patient and practitioner delay in diagnosis of upper gastrointestinal cancer

As knowledge on the causation of cancers advances and new treatments are developed, early recognition and accurate diagnosis becomes increasingly important. This review focused on identifying factors influencing patient and primary care practitioner delay for upper gastrointestinal cancer. A systematic methodology was applied, including extensive searches of the literature published from 1970 to 2003, systematic data extraction, quality assessment and narrative data synthesis. Included studies were those evaluating factors associated with the time interval between a patient first noticing a cancer symptom and presenting to primary care, between a patient first presenting to primary care and being referred to secondary care, or describing an intervention designed to reduce those intervals. Twenty-five studies were included in the review. Studies reporting delay intervals demonstrated that the patient phase of delay was greater than the practitioner phase, whilst patient-related research suggests that recognition of symptom seriousness is more important than recognition of the presence of the symptom. The main factors related to practitioner delay were misdiagnosis, application and interpretation of tests, and the confounding effect of existing disease. Greater understanding of patient factors is required, along with evaluation of interventions to ensure appropriate diagnosis, examination and investigation

Sexual function in Britain: Findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)

Background Despite its importance to sexual health and wellbeing, sexual function is given little attention in sexual health policy. Population-based studies are needed to understand sexual function across the life course. Methods We undertook a probability sample survey (the third National Survey of Sexual Attitudes and Lifestyles [Natsal-3]) of 15 162 individuals aged 16-74 years who lived in Britain (England, Scotland, and Wales). Interviews were done between Sept 6, 2010, and Aug 31, 2012. We assessed the distribution of sexual function by use of a novel validated measure (the Natsal-SF), which assessed problems with individual sexual response, sexual function in a relationship context, and self-appraisal of sex life (17 items; 16 items per gender). We assess factors associated with low sexual function (defi ned as the lowest quintile of distribution of Natsal-SF scores) and the distribution of components of the measure. Participants reporting one or more sexual partner in the past year were given a score on the Natsal-SF (11 690 participants). 4122 of these participants were not in a relationship for all of the past year and we employed the full information maximum likelihood method to handle missing data on four relationship items. Findings We obtained data for 4913 men and 6777 women for the Natsal-SF. For men and women, low sexual function was associated with increased age, and, after age-adjustment, with depression (adjusted odds ratio 3.70 [95% CI 2.90-4.72] for men and 4.11 [3.36-5.04] for women) and self-reported poor health status (2.63 [1.73-3.98] and 2.41 [1.72-3.39]). Low sexual function was also associated with experiencing the end of a relationship (1.52 [1.18-1.95] and 1.77 [1.44-2.17]), inability to talk easily about sex with a partner (2.36 [1.94-2.88] and 2.82 [2.28-3.48]), and not being happy in the relationship (2.89 [2.32-3.61] and 4.10 [3.39-4.97]). Associations were also noted with engaging in fewer than four sex acts in the past 4 weeks (3.13 [2.58-3.79] and 3.38 [2.80-4.09]), having had same sex partners (2.28 [1.56-3.35] and 1.60 [1.16-2.20]), paying for sex (in men only; 2.62 [1.46-4.71]), and higher numbers of lifetime sexual partners (in women only; 2.12 [1.68-2.67] for ten or more partners). Low sexual function was also associated with negative sexual health outcomes such as experience of non-volitional sex (1.98 [1.14-3.43] and 2.18 [1.79-2.66]) and STI diagnosis (1.50 [1.06-2.11] and 1.83 [1.35-2.47]). Among individuals reporting sex in the past year, problems with sexual response were common (41.6% of men and 51.2% of women reported one or more problem) but selfreported distress about sex lives was much less common (9.9% and 10.9%). For individuals in a sexual relationship for the past year, 23.4% of men and 27.4% of women reported an imbalance in level of interest in sex between partners, and 18.0% of men and 17.1% of women said that their partner had had sexual diffi culties. Most participants who did not have sex in the past year were not dissatisfi ed, distressed, or avoiding sex because of sexual diffi culties. Interpretation Wide variability exists in the distribution of sexual function scores. Low sexual function is associated with negative sexual health outcomes, supporting calls for a greater emphasis on sexual function in sexual health policy and interventions. Funding Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health