Investigating the influence of African American and African Caribbean race on primary care doctors' decision making about depression

This paper explores differences in how primary care doctors process the clinical presentation of depression by African American and African-Caribbean patients compared with white patients in the US and the UK. The aim is to gain a better understanding of possible pathways by which racial disparities arise in depression care. One hundred and eight doctors described their thought processes after viewing video recorded simulated patients presenting with identical symptoms strongly suggestive of depression. These descriptions were analysed using the CliniClass system, which captures information about micro-components of clinical decision making and permits a systematic, structured and detailed analysis of how doctors arrive at diagnostic, intervention and management decisions. Video recordings of actors portraying black (both African American and African-Caribbean) and white (both White American and White British) male and female patients (aged 55 years and 75 years) were presented to doctors randomly selected from the Massachusetts Medical Society list and from Surrey/South West London and West Midlands National Health Service lists, stratified by country (US v.UK), gender, and years of clinical experience (less v. very experienced). Findings demonstrated little evidence of bias affecting doctors' decision making processes, with the exception of less attention being paid to the potential outcomes associated with different treatment options for African American compared with White American patients in the US. Instead, findings suggest greater clinical uncertainty in diagnosing depression amongst black compared with white patients, particularly in the UK. This was evident in more potential diagnoses. There was also a tendency for doctors in both countries to focus more on black patients' physical rather than psychological symptoms and to identify endocrine problems, most often diabetes, as a presenting complaint for them. This suggests that doctors in both countries have a less well developed mental model of depression for black compared with white patients. © 2014 The Authors.

Recommendations for sex/gender neuroimaging research:key principles and implications for research design, analysis and interpretation

Neuroimaging (NI) technologies are having increasing impact in the study of complex cognitive and social processes. In this emerging field of social cognitive neuroscience, a central goal should be to increase the understanding of the interaction between the neurobiology of the individual and the environment in which humans develop and function. The study of sex/gender is often a focus for NI research, and may be motivated by a desire to better understand general developmental principles, mental health problems that show female-male disparities, and gendered differences in society. In order to ensure the maximum possible contribution of NI research to these goals, we draw attention to four key principles—overlap, mosaicism, contingency and entanglement—that have emerged from sex/gender research and that should inform NI research design, analysis and interpretation. We discuss the implications of these principles in the form of constructive guidelines and suggestions for researchers, editors, reviewers and science communicators.

Linear binocular combination of responses to contrast modulation:contrast-weighted summation in first- and second-order vision

Binocular combination for first-order (luminancedefined) stimuli has been widely studied, but we know rather little about this binocular process for spatial modulations of contrast (second-order stimuli). We used phase-matching and amplitude-matching tasks to assess binocular combination of second-order phase and modulation depth simultaneously. With fixed modulation in one eye, we found that binocularly perceived phase was shifted, and perceived amplitude increased almost linearly as modulation depth in the other eye increased. At larger disparities, the phase shift was larger and the amplitude change was smaller. The degree of interocular correlation of the carriers had no influence. These results can be explained by an initial extraction of the contrast envelopes before binocular combination (consistent with the lack of dependence on carrier correlation) followed by a weighted linear summation of second-order modulations in which the weights (gains) for each eye are driven by the first-order carrier contrasts as previously found for first-order binocular combination. Perceived modulation depth fell markedly with increasing phase disparity unlike previous findings that perceived first-order contrast was almost independent of phase disparity. We present a simple revision to a widely used interocular gain-control theory that unifies first- and second-order binocular summation with a single principle-contrast-weighted summation-and we further elaborate the model for first-order combination. Conclusion: Second-order combination is controlled by first-order contrast.

How doctors' communication style and race concordance influence African-Caribbean patients when disclosing depression

Objective: To determine the impact of doctors' communication style and doctor-patient race concordance on UK African-Caribbeans' comfort in disclosing depression. Methods: 160 African-Caribbean and 160 white British subjects, stratified by gender and history of depression, participated in simulated depression consultations with video-recorded doctors. Doctors were stratified by black or white race, gender and a high (HPC) or low patient-centred (LPC) communication style, giving a full 2. ×. 2. ×. 2 factorial design. Afterwards, participants rated aspects of doctors' communication style, their comfort in disclosing depression and treatment preferences. Results: Race concordance had no impact on African-Caribbeans' comfort in disclosing depression. However a HPC versus LPC communication style made them significantly more positive about their interactions with doctors (p = 0.000), their overall comfort (p = 0.003), their comfort in disclosing their emotional state (p = 0.001), and about considering talking therapy (p = 0.01); but less positive about considering antidepressant medication (p =0.01). Conclusion: Doctors' communication style was shown to be more important than patient race or race concordance in influencing African Caribbeans' depression consultation experiences. Changing doctors' communication style may help reduce disparities in depression care. Practice Implications: Practitioners should cultivate a HPC style to make African-Caribbeans more comfortable when disclosing depression, so that it is less likely to be missed.

Encouraging majority support for immigrant access to health services:multiple categorization and social identity complexity as antecedents of health equality

Health disparities between groups remain even after accounting for established causes such as structural and economic factors. The present research tested, for the first time, whether multiple social categorization processes can explain enhanced support for immigrant health (measured by respondents’ behavioral intention to support immigrants’ vaccination against A H1N1 disease by cutting regional public funds). Moreover, the mediating role of individualization and the moderating role of social identity complexity were tested. Findings showed that multiple versus single categorization of immigrants lead to support their right to health and confirmed the moderated mediation hypothesis. The potential in developing this sort of social cognitive intervention to address health disparities is discussed.

An analysis and comparison of commonly available United Kingdom prescribing resources

Background and objective: Safe prescribing requires accurate and practical information about drugs. Our objective was to measure the utility of current sources of prescribing guidance when used to inform practical prescribing decisions, and to compare current sources of prescribing guidance in the UK with idealized prescribing guidance. Methods: We developed 25 clinical scenarios. Two independent assessors rated and ranked the performance of five common sources of prescribing guidance in the UK when used to answer the clinical scenarios. A third adjudicator facilitated review of any disparities. An idealized list of contents for prescribing guidance was developed and sent for comments to academics and users of prescribing guidance. Following consultation an operational check was used to assess compliance with the idealized criteria. The main outcome measures were relative utility in answering the clinical scenarios and compliance with the idealized prescribing guidance. Results: Current sources of prescribing guidance used in the UK differ in their utility, when measured using clinical scenarios. The British National Formulary (BNF) and EMIS LV were the best performing sources in terms of both ranking [mean rank 1·24 and 2·20] and rating [%excellent or adequate 100% and 72%]. Current sources differed in the extent to which they fulfilled criteria for ideal prescribing guidance, but the BNF, and EMIS LV to a lesser extent, closely matched the criteria. Discussion: We have demonstrated how clinical scenarios can be used to assess prescribing guidance resources. Producers of prescribing guidance documents should consider our idealized template. Prescribers require high-quality information to support their practice. Conclusion: Our test was helpful in distinguishing between prescribing resources. Producers of prescribing guidance should consider the utility of their products to end-users, particularly in those more complex areas where prescribers may need most support. Existing UK prescribing guidance resources differ in their ability to provide assistance to prescribers. © 2010 Blackwell Publishing Ltd.

Clinical significance of medication reconciliation in children admitted to a UK pediatric hospital:observational study of neurosurgical patients

Background: In December 2007, the National Institute for Health and Clinical Excellence and the National Patient Safety Agency in the UK (NICE-NPSA) published guidance that recommends all adults admitted to hospital receive medication reconciliation, usually by pharmacy staff. A costing and report tool was provided indicating a resource requirement of d12.9 million for England per year. Pediatric patients are excluded from this guidance. Objective: To determine the clinical significance of medication reconciliation in children on admission to hospital. Methods: A prospective observational study included pediatric patients admitted to a neurosurgical ward at Birmingham Childrens Hospital, Birmingham, England, between September 2006 and March 2007. Medication reconciliation was conducted by a pharmacist after the admission of each of 100 consecutive eligible patients aged 4 months to 16 years. The clinical significance of prescribing disparities between pre-admission medications and initial admission medication orders was determined by an expert multidisciplinary panel and quantified using an analog scale. The main outcome measure was the clinical signficance of unintentional variations between hospital admission medication orders and physician-prescribed pre-admission medication for repeat (continuing) medications. Results: Initial admission medication orders for children differed from prescribed pre-admission medication in 39%of cases. Half of all resulting prescribing variations in this setting had the potential to cause moderate or severe discomfort or clinical deterioration. These results mirror findings for adults. Conclusions: The introduction of medication reconciliation in children on admission to hospital has the potential to reduce discomfort or clinical deterioration by reducing unintentional changes to repeat prescribed medication. Consequently, there is no justification for the omission of children from the NICENPSA guidance concerning medication reconciliation in hospitals, and costing tools should include pediatric patients. © 2010 Adis Data Information BV. All rights reserved.

Early spatial vision:a view through two eyes

Simple features such as edges are the building blocks of spatial vision, and so I ask: how arevisual features and their properties (location, blur and contrast) derived from the responses ofspatial filters in early vision; how are these elementary visual signals combined across the twoeyes; and when are they not combined? Our psychophysical evidence from blur-matchingexperiments strongly supports a model in which edges are found at the spatial peaks ofresponse of odd-symmetric receptive fields (gradient operators), and their blur B is givenby the spatial scale of the most active operator. This model can explain some surprisingaspects of blur perception: edges look sharper when they are low contrast, and when theirlength is made shorter. Our experiments on binocular fusion of blurred edges show that singlevision is maintained for disparities up to about 2.5*B, followed by diplopia or suppression ofone edge at larger disparities. Edges of opposite polarity never fuse. Fusion may be served bybinocular combination of monocular gradient operators, but that combination - involvingbinocular summation and interocular suppression - is not completely understood.In particular, linear summation (supported by psychophysical and physiological evidence)predicts that fused edges should look more blurred with increasing disparity (up to 2.5*B),but results surprisingly show that edge blur appears constant across all disparities, whetherfused or diplopic. Finally, when edges of very different blur are shown to the left and righteyes fusion may not occur, but perceived blur is not simply given by the sharper edge, nor bythe higher contrast. Instead, it is the ratio of contrast to blur that matters: the edge with theAbstracts 1237steeper gradient dominates perception. The early stages of binocular spatial vision speak thelanguage of luminance gradients.

Binocular summation, binocular fusion and the transition to diplopia

The visual system combines spatial signals from the two eyes to achieve single vision. But if binocular disparity is too large, this perceptual fusion gives way to diplopia. We studied and modelled the processes underlying fusion and the transition to diplopia. The likely basis for fusion is linear summation of inputs onto binocular cortical cells. Previous studies of perceived position, contrast matching and contrast discrimination imply the computation of a dynamicallyweighted sum, where the weights vary with relative contrast. For gratings, perceived contrast was almost constant across all disparities, and this can be modelled by allowing the ocular weights to increase with disparity (Zhou, Georgeson & Hess, 2014). However, when a single Gaussian-blurred edge was shown to each eye perceived blur was invariant with disparity (Georgeson & Wallis, ECVP 2012) – not consistent with linear summation (which predicts that perceived blur increases with disparity). This blur constancy is consistent with a multiplicative form of combination (the contrast-weighted geometric mean) but that is hard to reconcile with the evidence favouring linear combination. We describe a 2-stage spatial filtering model with linear binocular combination and suggest that nonlinear output transduction (eg. ‘half-squaring’) at each stage may account for the blur constancy.

The integration of ProxiMAX randomisation with CIS display for the production of novel peptides

Saturation mutagenesis is a powerful tool in modern protein engineering, which permits key residues within a protein to be targeted in order to potentially enhance specific functionalities. However, the creation of large libraries using conventional saturation mutagenesis with degenerate codons (NNN or NNK/S) has inherent redundancy and consequent disparities in codon representation. Therefore, both chemical (trinucleotide phosphoramidites) and biological methods (sequential, enzymatic single codon additions) of non-degenerate saturation mutagenesis have been developed in order to combat these issues and so improve library quality. Large libraries with multiple saturated positions can be limited by the method used to screen them. Although the traditional screening method of choice, cell-dependent methods, such as phage display, are limited by the need for transformation. A number of cell-free screening methods, such as CIS display, which link the screened phenotype with the encoded genotype, have the capability of screening libraries with up to 1014 members. This thesis describes the further development of ProxiMAX technology to reduce library codon bias and its integration with CIS display to screen the resulting library. Synthetic MAX oligonucleotides are ligated to an acceptor base sequence, amplified, and digested, subsequently adding a randomised codon to the acceptor, which forms an iterative cycle using the digested product of the previous cycle as the base sequence for the next. Initial use of ProxiMAX highlighted areas of the process where changes could be implemented in order to improve the codon representation in the final library. The refined process was used to construct a monomeric anti-NGF peptide library, based on two proprietary dimeric peptides (Isogenica) that bind NGF. The resulting library showed greatly improved codon representation that equated to a theoretical diversity of ~69%. The library was subsequently screened using CIS display and the discovered peptides assessed for NGF-TrkA inhibition by ELISA. Despite binding to TrkA, these peptides showed lower levels of inhibition of the NGF-TrkA interaction than the parental dimeric peptides, highlighting the importance of dimerization for inhibition of NGF-TrkA binding.