State based model of long-term potentiation and synaptic tagging and capture

Recent data indicate that plasticity protocols have not only synapse-specific but also more widespread effects. In particular, in synaptic tagging and capture (STC), tagged synapses can capture plasticity-related proteins, synthesized in response to strong stimulation of other synapses. This leads to long-lasting modification of only weakly stimulated synapses. Here we present a biophysical model of synaptic plasticity in the hippocampus that incorporates several key results from experiments on STC. The model specifies a set of physical states in which a synapse can exist, together with transition rates that are affected by high- and low-frequency stimulation protocols. In contrast to most standard plasticity models, the model exhibits both early- and late-phase LTP/D, de-potentiation, and STC. As such, it provides a useful starting point for further theoretical work on the role of STC in learning and memory

Effective connectivity reveals strategy differences in an expert calculator

Mathematical reasoning is a core component of cognition and the study of experts defines the upper limits of human cognitive abilities, which is why we are fascinated by peak performers, such as chess masters and mental calculators. Here, we investigated the neural bases of calendrical skills, i.e. the ability to rapidly identify the weekday of a particular date, in a gifted mental calculator who does not fall in the autistic spectrum, using functional MRI. Graph-based mapping of effective connectivity, but not univariate analysis, revealed distinct anatomical location of “cortical hubs” supporting the processing of well-practiced close dates and less-practiced remote dates: the former engaged predominantly occipital and medial temporal areas, whereas the latter were associated mainly with prefrontal, orbitofrontal and anterior cingulate connectivity. These results point to the effect of extensive practice on the development of expertise and long term working memory, and demonstrate the role of frontal networks in supporting performance on less practiced calculations, which incur additional processing demands. Through the example of calendrical skills, our results demonstrate that the ability to perform complex calculations is initially supported by extensive attentional and strategic resources, which, as expertise develops, are gradually replaced by access to long term working memory for familiar material

Medical communication and technology: a video-based process study of the use of decision aids in primary care

Background: much of the research on decision-making in health care has focused on consultation outcomes. Less is known about the process by which clinicians and patients come to a treatment decision. This study aimed to quantitatively describe the behaviour shown by doctors and patients during primary care consultations when three types of decision aids were used to promote treatment decision-making in a randomised controlled trial.Methods: a video-based study set in an efficacy trial which compared the use of paper-based guidelines (control) with two forms of computer-based decision aids (implicit and explicit versions of DARTS II). Treatment decision concerned warfarin anti-coagulation to reduce the risk of stroke in older patients with atrial fibrillation. Twenty nine consultations were video-recorded. A ten-minute 'slice' of the consultation was sampled for detailed content analysis using existing interaction analysis protocols for verbal behaviour and ethological techniques for non-verbal behaviour.Results: median consultation times (quartiles) differed significantly depending on the technology used. Paper-based guidelines took 21 (19–26) minutes to work through compared to 31 (16–41) minutes for the implicit tool; and 44 (39–55) minutes for the explicit tool. In the ten minutes immediately preceding the decision point, GPs dominated the conversation, accounting for 64% (58–66%) of all utterances and this trend was similar across all three arms of the trial. Information-giving was the most frequent activity for both GPs and patients, although GPs did this at twice the rate compared to patients and at higher rates in consultations involving computerised decision aids. GPs' language was highly technically focused and just 7% of their conversation was socio-emotional in content; this was half the socio-emotional content shown by patients (15%). However, frequent head nodding and a close mirroring in the direction of eye-gaze suggested that both parties were active participants in the conversationConclusion: irrespective of the arm of the trial, both patients' and GPs' behaviour showed that they were reciprocally engaged in these consultations. However, even in consultations aimed at promoting shared decision-making, GPs' were verbally dominant, and they worked primarily as information providers for patients. In addition, computer-based decision aids significantly prolonged the consultations, particularly the later phases. These data suggest that decision aids may not lead to more 'sharing' in treatment decision-making and that, in their current form, they may take too long to negotiate for use in routine primary car

Bowel cancer screening in England: a qualitative study of GPs' attitudes and information needs

BACKGROUND: The National Health Service Bowel Cancer Screening Programme is to be introduced in England during 2006. General Practitioners are a potentially important point of contact for participants throughout the screening process. The aims of the study were to examine GPs' attitudes and information needs with regard to bowel cancer screening, with a view to developing an information pack for primary care teams that will be circulated prior to the introduction of the programme. METHODS: 32 GPs participated in semi-structured telephone interviews. 18 of these had participated in the English Bowel Screening Pilot, and 14 had not. Interviews covered attitudes towards the introduction of the Bowel Cancer Screening Programme, expected or actual increases in workload, confidence in promoting informed choice, and preferences for receiving information about the programme. RESULTS: GPs in the study were generally positive about the introduction of the Bowel Cancer Screening Programme. A number of concerns were identified by GPs who had not taken part in the pilot programme, particularly relating to patient welfare, patient participation, and increased workload. GPs who had taken part in the pilot reported holding similar concerns prior to their involvement. However, in many cases these concerns were not confirmed through GPs experiences with the pilot. A number of specific information needs were identified by GPs to enable them to provide a supportive role to participants in the programme. CONCLUSION: The study has found considerable GP support for the introduction of the new Bowel Cancer Screening Programme. Nonetheless, GPs hold some significant reservations regarding the programme. It is important that the information needs of GPs and other members of the primary care team are addressed prior to the roll-out of the programme so they are equipped to promote informed choice and provide support to patients who consult them with queries regarding screening

Factors influencing research engagement: research interest, confidence and experience in an Australian speech-language pathology workforce

Background: Recent initiatives within an Australia public healthcare service have seen a focus on increasing the research capacity of their workforce. One of the key initiatives involves encouraging clinicians to be research generators rather than solely research consumers. As a result, baseline data of current research capacity are essential to determine whether initiatives encouraging clinicians to undertake research have been effective. Speech pathologists have previously been shown to be interested in conducting research within their clinical role; therefore they are well positioned to benefit from such initiatives. The present study examined the current research interest, confidence and experience of speech language pathologists (SLPs) in a public healthcare workforce, as well as factors that predicted clinician research engagement

Dual equipoise shared decision making: definitions for decision and behaviour support interventions

Contains fulltext : 80919.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: There is increasing interest in interventions that can support patients who face difficult decisions and individuals who need to modify their behaviour to achieve better outcomes. Evidence for effectiveness is used to categorise patients care. Effective care is where evidence of benefit outweighs harm: patients should always receive this type of care, where indicated. Preference-sensitive care describes a situation where the evidence for the superiority of one treatment over another is either not available or does not allow differentiation; in this situation, there are two or more valid approaches, and the best choice depends on how individuals value the risks and benefits of treatments. DISCUSSION: Preference-sensitive decisions are defined by equipoise: situations where options need to be deliberated. Moreover, where both healthcare professionals and patients agree that equipoise exists, situations may be regarded as having 'dual equipoise'. Such conditions are ideal for shared decision making. However, there are many situations in medicine where dual equipoise does not exist, where health professionals hold the view that scientific evidence for benefit strongly outweighs harm. This is often the case where people suffer from chronic conditions, and where behaviour change is recommended to improve outcomes. However, some patients, are either ambivalent or find it difficult to sustain optimal behaviours, i.e., patients will be in varying degrees of equipoise. Therefore, situations where dual equipoise exists (or not) help to clarify the definitions of two classes of support, namely, decision and behaviour change support interventions. Decision support interventions help people think about choices they face; they describe where and why choice exists, in short, conditions of dual equipoise; they provide information about options, including, where reasonable, the option of taking no action. These interventions help people to deliberate, independently or in collaboration with others, about options by considering relevant attributes; they support people to forecast how they might feel about short, intermediate, and long-term outcomes that have relevant consequences, in ways that help the process of constructing preferences and eventual decision making appropriate to their individual situation. Whereas, behavioural support interventions describe, justify, and recommend actions that, over time, lead to predictable outcomes over short, intermediate, and long-term timeframes, and that have relevant and important consequences for those who are considering behaviour change. SUMMARY: Decision and behaviour support interventions have divergent aims, different relationships to equipoise, and form two classes of interventions

Economics methods in Cochrane systematic reviews of health promotion and public health related interventions.

Peer reviewedPublisher PD

What have transgenic and knockout animals taught us about respiratory disease?

Over the past decade there has been a significant shift to the use of murine models for investigations into the molecular basis of respiratory diseases, including asthma and chronic obstructive pulmonary disease. These models offer the exciting prospect of dissecting the complex interaction between cytokines, chemokines and growth related peptides in disease pathogenesis. Furthermore, the receptors and the intracellular signalling pathways that are subsequently activated are amenable for study because of the availability of monoclonal antibodies and techniques for targeted gene disruption and gene incorporation for individual mediators, receptors and proteins. However, it is clear that extrapolation from these models to the human condition is not straightforward, as reflected by some recent clinical disappointments. This is not necessarily a problem with the use of mice itself, but results from our continued ignorance of the disease process and how to improve the modelling of complex interactions between different inflammatory mediators that underlie clinical pathology. This review highlights some of the strengths and weaknesses of murine models of respiratory disease