Managing expectational language: translational genetic professionals consider the clinical potential of next-generation sequencing technologies

Clinical genetic professionals are used to being flooded by claims about the seemingly endless potential and promise of next-generation sequencing (NGS) in medicine today. This paper is about managing expectations in translational medicine. From 2009 to 2011, we conducted focus groups with genetic and allied professionals concerned with genomics in the clinic to examine their attitudes and perspectives of genetic and genomic tools in this environment. In this paper, we examine and explore some of their discussions, specifically related to NGS and whole genome sequencing tests and their introduction as normal clinical tools. Informed by sociology of expectations (SE), we discuss expectational language in the arena of translational medicine. Through SE, illuminated are some barriers and strategies used by professionals to manage expectations. Further, our work suggests the importance of SE and more nuanced study to understand the discursive realm of translational genomic medicine.     

Anything you can do, you can do better: neural substrates of incentive-based performance enhancement

Performance-based pay schemes in many organizations share the fundamental assumption that the performance level for a given task will increase as a function of the amount of incentive provided. Consistent with this notion, psychological studies have demonstrated that expectations of reward can improve performance on a plethora of different cognitive and physical tasks, ranging from problem solving to the voluntary regulation of heart rate. However, much less is understood about the neural mechanisms of incentivized performance enhancement. In particular, it is still an open question how brain areas that encode expectations about reward are able to translate incentives into improved performance across fundamentally different cognitive and physical task requirements.     

Cooperation and deception recruit different subsets of the theory-of-mind network

The term "theory of mind" (ToM) describes an evolved psychological mechanism that is necessary to represent intentions and expectations in social interaction. It is thus involved in determining the proclivity of others to cooperate or defect. While in cooperative settings between two parties the intentions and expectations of the protagonists match, they diverge in deceptive scenarios, in which one protagonist is intentionally manipulated to hold a false belief about the intention of the other. In a functional magnetic resonance imaging paradigm using cartoons showing social interactions (including the outcome of the interaction) between two or three story characters, respectively, we sought to determine those brain areas of the ToM network involved in reasoning about cooperative versus deceptive interactions. Healthy volunteers were asked to reflect upon the protagonists' intentions and expectations in cartoons depicting cooperation, deception or a combination of both, where two characters cooperated to deceive a third. Reasoning about the mental states of the story characters yielded substantial differences in activation patterns: both deception and cooperation activated bilateral temporoparietal junction, parietal and cingulate regions, while deception alone additionally recruited orbitofrontal and medial prefrontal regions. These results indicate an important role for prefrontal cortex in processing a mismatch between a character's intention and another's expectations as required in complex social interactions.     

Weight loss expectations and goals in a population sample of overweight and obese US adults

The purpose of this study was to investigate weight loss expectations and goals in a population sample of US adults who planned to make a weight loss attempt, and to examine predictors of those expectations and goals. Participants were 658 overweight and obese adults (55% women, mean age = 47.9 years, BMI = 31.8 kg/m(2)) who responded to a telephone survey about weight loss. Respondents reported weight loss expectations (i.e., reductions they realistically expected) and goals (i.e., reductions they ideally desired) for an upcoming "serious and deliberate" weight loss attempt. They also reported the expectations they had, and the reductions they actually achieved, in a previous attempt. Respondents' weight loss expectations for their upcoming attempt (8.0% reduction in initial weight) were significantly more modest than their goals for that attempt (16.8%), and smaller than the losses that they expected (12.0%), and achieved (8.9%) in their most recent past attempt (Ps 相似文献   

Mothering, Work, and Gender in Urban Asante Ideology and Practice

Conventional Asante gender roles in Ghana emphasize biological motherhood for women, but Asante assume mothers' loyalties and schedule conflicts will interfere with equally female gendered expectations within marriage, not with fulltime paid work. Asante express their maternal devotion most by working tirelessly to meet their children's financial needs, not by staying home with them. In this paper I analyze urban Asante ideals and practices about gender and parenting, drawing on life histories and fieldwork with Kumasi traders since 1978. Market trading is ideal "nursing-mother work" because it generates the steady income needed to raise children successfully to adulthood, not because it is compatible with childcare. Marriage depends directly on women's intimate domestic work, creating structural tension with motherhood. Concepts about motherly fathers, manly women, and fools of both genders show how the distribution of income and capital defines gender and kin role performance. Asante have accommodated historical changes in gender expectations about work, parenihood, and marriage within their general positive emphasis on negotiability and renegoiiability of relationship content, [ gender, work, Asante, traders, parenting ]     

Management and outcome of winter upper respiratory tract infections in children aged 0-9 years.

Age-specific incidences for upper respiratory tract infections in children from a new-town population during 1975-7 were studied, and 965 consecutive upper respiratory tract infections in children aged under 10 during two winters were analysed in detail. Significantly different management plans made by seven doctors did not correlate with the clinical outcome as judged by complications, recall rates, and demand for treatment for similar episodes in the future. Two hundred and thirty-two children (24%) returned for another consultation for the same episode of upper respiratory tract infection. The main reason for these repeat consultations seemed to be that parental expectations about the natural history of the illness were not fulfilled. More realistic parental expectations might be set and safer clinical standards maintained if doctors warned parents about symptoms such as cough and occasional diarrhoea or vomiting that are commonly associated with upper respiratory tract infections in children.     

Lessons learned from placebo groups in antidepressant trials

This comprehensive review provides an overview about placebo and nocebo phenomena in antidepressant trials. Improvements in the placebo groups may partly be explained through methodological issues such as natural course of depression and regression to the mean, but also fundamentally reflect investigators' and participants' expectations. A meta-analysis by our group of 96 randomized placebo-controlled trials showed large placebo responses to antidepressant medication. Moderator analyses revealed substantially larger placebo responses in observer ratings compared with self-report. Effect sizes in observer ratings showed strong increase with publication year while this effect was not found for patients' self-ratings. This reflects the strong influence of investigators' expectations. The analysis of 'nocebo effects', e.g. adverse effects in placebo groups of antidepressant trials also confirms the impact of expectations: nocebo symptoms reflected the typical side-effect patterns expected in the drug group, with higher symptoms rates in the placebo groups of tricyclic antidepressant trials compared with placebo groups of trials testing selective serotonin reuptake inhibitors. While the placebo response seems to be similar for women and men, gender differences were found for nocebo rates. In the conclusion, we discuss potential implications for clinical trial designs and argue for interventions aimed at optimizing positive expectations of treatment benefit while minimizing the impact of adverse effects.     

Dogs' looking times and pupil dilation response reveal expectations about contact causality

Contact causality is one of the fundamental principles allowing us to make sense of our physical environment. From an early age, humans perceive spatio-temporally contiguous launching events as causal. Surprisingly little is known about causal perception in non-human animals, particularly outside the primate order. Violation-of-expectation paradigms in combination with eye-tracking and pupillometry have been used to study physical expectations in human infants. In the current study, we establish this approach for dogs (Canis familiaris). We presented dogs with realistic three-dimensional animations of launching events with contact (regular launching event) or without contact between the involved objects. In both conditions, the objects moved with the same timing and kinematic properties. The dogs tracked the object movements closely throughout the study but their pupils were larger in the no-contact condition and they looked longer at the object initiating the launch after the no-contact event compared to the contact event. We conclude that dogs have implicit expectations about contact causality.     

A neural representation of prior information during perceptual inference

Perceptual inference is biased by foreknowledge about what is probable or possible. How prior expectations are neurally represented during visual perception, however, remains unknown. We used functional magnetic resonance imaging to measure brain activity in humans judging simple visual stimuli. Perceptual decisions were either biased in favor of a single alternative (A/ approximately A decisions) or taken without bias toward either choice (A/B decisions). Extrastriate and anterior temporal lobe regions were more active during A/ approximately A than A/B decisions, suggesting multiple representations of prior expectations within the visual hierarchy. Forward connectivity was increased when expected and observed perception diverged ("prediction error" signals), whereas prior expectations fed backward from higher to lower regions. Finally, the coincidence between expected and observed perception activated orbital prefrontal regions, perhaps reflecting the reinforcement of prior expectations. These data support computational and quantitative models proposing that a visual percept emerges from converging bottom-up and top-down signals.     

An Exploration of the Factors Considered When Forming Expectations for Returning to Work following Sickness Absence Due to a Musculoskeletal Condition

Introduction

Workers’ own expectations for returning to work following a period of sickness absence have been found to be one of the best predictors of future work status; however, there is a limited understanding of why people expect what they do. The current study was undertaken with the aim of determining what people take into consideration when forming their expectations for returning to work.

Methods

Thirty-four people (8 women, 26 men), who were off work due to a musculoskeletal condition, participated in one of 14 focus groups. Participants were aged 25 to 65 (M = 45, SD = 12.6), and all had been out of work for 3 months or less.

Results

All participants reported expecting to return to work, with the most common timeframe being approximately 30 days (Range = 1 day-12 months). When explaining what they thought about when forming their expectations, participants referenced numerous considerations. Much of what was spoken about could be compartmentalized to reflect features of themselves, their condition, or their broader environmental contexts. Participant’s subjective experience of these features influenced his or her expectations. Prominent themes included concerns about employability, a desire to get back to normal, no job to go back to, mixed emotions, re-injury concerns, the judgments of workplace stakeholders, being needed by their employer, waiting for input, until the money runs out, and working out what was in their best interest.

Conclusions

Indications are that many of the reported considerations are amenable to intervention, suggesting opportunities to assist workers in the process of returning to work.     

How blind is double-blind? A study of fish oil versus placebo

The distinctive aftertaste associated with fish oil preparations used in clinical trials of omega-3 fatty acids may weaken the double-blind. This double-blind pilot study was designed to examine whether normal subjects could correctly 'guess' if they were receiving capsules containing concentrated fish oil or capsules of pure olive oil. The informed consent was designed to give subjects ambiguous expectations about what oil they might be receiving to examine whether this would influence their guess. Despite a marked difference in taste experience, there was no significant difference in correct guesses between the two groups. The results suggest that altering subjects' expectations could further improve the validity of the double-blind.     

Interprofessional Collaboration on an Internal Medicine Ward: Role Perceptions and Expectations among Nurses and Residents

Background

Effective interprofessional collaboration requires that team members share common perceptions and expectations of each other''s roles.

Objective

Describe and compare residents’ and nurses’ perceptions and expectations of their own and each other’s professional roles in the context of an Internal Medicine ward.

Methods

A convenience sample of 14 residents and 14 nurses volunteers from the General Internal Medicine Division at the University Hospitals of Geneva, Switzerland, were interviewed to explore their perceptions and expectations of residents’ and nurses’ professional roles, for their own and the other profession. Interviews were analysed using thematic content analysis. The same respondents also filled a questionnaire asking their own intended actions and the expected actions from the other professional in response to 11 clinical scenarios.

Results

Three main themes emerged from the interviews: patient management, clinical reasoning and decision-making processes, and roles in the team. Nurses and residents shared general perceptions about patient management. However, there was a lack of shared perceptions and expectations regarding nurses’ autonomy in patient management, nurses’ participation in the decision-making process, professional interdependence, and residents’ implication in teamwork. Results from the clinical scenarios showed that nurses’ intended actions differed from residents’ expectations mainly regarding autonomy in patient management. Correlation between residents’ expectations and nurses’ intended actions was 0.56 (p = 0.08), while correlation between nurses’ expectations and residents’ intended actions was 0.80 (p<0.001).

Conclusions

There are discordant perceptions and unmet expectations among nurses and residents about each other’s roles, including several aspects related to the decision-making process. Interprofessional education should foster a shared vision of each other’s roles and clarify the boundaries of autonomy of each profession.     

The mode of evolution of molecular markers in populations of house mice under artificial selection for locomotor behavior

A complete understanding of the mode of evolution of molecular markers is important for making inferences about different population genetic parameters, especially because a number of studies have reported patterns of allelic variation at molecular markers that are not in agreement with neutral evolutionary expectations. In the present study, house mice (Mus domesticus) from the fourteenth generation of a selection experiment for increased voluntary wheel-running activity were used to test how selection on a complex behavior affects the distribution of allelic variation by examining patterns of variation at six microsatellite and four allozyme loci. This population had a hierarchical structure that allowed for simultaneous testing of the effects of selection and genetic drift on the distribution of allelic variation by comparing observed patterns of allele frequencies and estimates of genetic divergence at multiple hierarchical levels to expectations under models of neutral evolution. The levels of genetic divergence among replicate lines and between selection groups, estimated from microsatellite data or pooled microsatellite and allozyme data, were not significantly different from expectations under neutral evolution. Furthermore, the pattern of change of allele frequencies between the base population and generation 14 was largely in agreement with expectations under neutral evolution (although the PGM locus exhibited a pattern of change within populations that was difficult to explain under neutral evolution). Overall the results generally provide support for the neutral evolution of molecular markers.     

Using self‐portrait photographs to understand self‐concepts of Chinese and American university students

This study examines differences between self‐concepts of Chinese and American university students. Both groups used 35mm cameras to show who they are. They wrote statements about the intended meaning of their best photo. The signs of other people, materials, and objects, and cultural ideas in each photograph were analyzed. Contrary to expectations, a higher percentage of Chinese students portrayed themselves as independent, and a higher percentage of Americans were oriented to other people. Consistent with expectations, Americans were more likely to be oriented towards materials and objects. Both groups were equally likely to be oriented towards cultural ideas.     

Rooks perceive support relations similar to six-month-old babies

Some corvids have demonstrated cognitive abilities that rival or exceed those of the great apes; for example, tool use in New Caledonian crows, and social cognition, episodic-like memory and future planning in Western scrub-jays. Rooks appear to be able to solve novel tasks through causal reasoning rather than simple trial-and-error learning. Animals with certain expectations about how objects interact would be able to narrow the field of candidate causes substantially, because some causes are simply ‘impossible’. Here we present evidence that rooks hold such expectations and appear to possess perceptual understanding of support relations similar to that demonstrated by human babies, which is more comprehensive than that of chimpanzees.     

The myth of the biotech revolution

The existence of a medicinal 'biotech revolution' has been widely accepted and promoted by academics, consultants, industry and government. This has generated expectations about significant improvements in the drug discovery process, healthcare and economic development that influence a considerable amount of policy-making. Here we present empirical evidence, from a variety of indicators, that shows that a range of outputs have failed to keep pace with increased research and development spending. Rather than producing revolutionary changes, medicinal biotechnology is following a well-established pattern of slow and incremental technology diffusion. Consequently, many expectations are wildly optimistic and over-estimate the speed and extent of the impact of biotechnology, suggesting that the assumptions underpinning much contemporary policymaking need to be rethought.     

Fears and Beliefs in Rheumatoid Arthritis and Spondyloarthritis: A Qualitative Study

ObjectivesTo explore beliefs and apprehensions about disease and its treatment in patients with rheumatoid arthritis and spondyloarthritis.Methods25 patients with rheumatoid arthritis and 25 with spondyloarthritis participated in semi-structured interviews about their disease and its treatment. The interviews were performed by trained interviewers in participants'' homes. The interviews were recorded and the main themes identified by content analysis.ResultsPatients differentiated between the underlying cause of the disease, which was most frequently identified as a hereditary or individual predisposition. In patients with rheumatoid arthritis, the most frequently cited triggering factor for disease onset was a psychological factor or life-event, whereas patients with spondyloarthritis tended to focus more on an intrinsic vulnerability to disease. Stress and overexertion were considered important triggering factors for exacerbations, and relaxation techniques were frequently cited strategies to manage exacerbations. The unpredictability of the disease course was a common source of anxiety. Beliefs about the disease and apprehensions about the future tended to evolve over the course of the disease, as did treatment expectations.ConclusionsPatients with rheumatoid arthritis and spondyloarthritis hold a core set of beliefs and apprehensions that reflect their level of information about their disease and are not necessarily appropriate. The physician can initiate discussion of these beliefs in order to dispel misconceptions, align treatment expectations, provide reassurance to the patient and readjust disease management. Such a dialogue would help improve standards of care in these chronic and incapacitating diseases.     

Distribution of sibship size in families manifesting a genetically determined disorder.

The effect on sibship size distribution of the birth of a child with a genetical defect is considered for several different conditions. Family size continues to be over-dispersed in such cases, rather than showing any sign of reduced variation, though theoretical expectations about the correlation between numbers of normal and affected children are not well-supported by the data.     

Task-induced neural covariability as a signature of approximate Bayesian learning and inference

Perception is often characterized computationally as an inference process in which uncertain or ambiguous sensory inputs are combined with prior expectations. Although behavioral studies have shown that observers can change their prior expectations in the context of a task, robust neural signatures of task-specific priors have been elusive. Here, we analytically derive such signatures under the general assumption that the responses of sensory neurons encode posterior beliefs that combine sensory inputs with task-specific expectations. Specifically, we derive predictions for the task-dependence of correlated neural variability and decision-related signals in sensory neurons. The qualitative aspects of our results are parameter-free and specific to the statistics of each task. The predictions for correlated variability also differ from predictions of classic feedforward models of sensory processing and are therefore a strong test of theories of hierarchical Bayesian inference in the brain. Importantly, we find that Bayesian learning predicts an increase in so-called “differential correlations” as the observer’s internal model learns the stimulus distribution, and the observer’s behavioral performance improves. This stands in contrast to classic feedforward encoding/decoding models of sensory processing, since such correlations are fundamentally information-limiting. We find support for our predictions in data from existing neurophysiological studies across a variety of tasks and brain areas. Finally, we show in simulation how measurements of sensory neural responses can reveal information about a subject’s internal beliefs about the task. Taken together, our results reinterpret task-dependent sources of neural covariability as signatures of Bayesian inference and provide new insights into their cause and their function.