Modulatory actions of the neuropeptide FMRFamide on synaptic transmission in Helisoma neurons

In these studies, the inhibitory effects of a neuropeptide, FMRFamide, on synaptic transmission was examined. A model system of cultured synapses was used to investigate the subcellular mechanisms underlying the action of FMRFamide. In this model system, a unidirectional synapse forms between somata of two identified neurons, B5 and B19. This offers several advantages, the main one being the large size of the synaptic terminals which allows for electrophysiological access to both elements of the synapse as well as control over the intracellular and extracellular environments of the neurons;FMRFamide is endogenous to Helisoma and has widespread effects on molluscan neurons. The magnitude of the action potential-evoked postsynaptic potential was reduced in the presence of FMRFamide. Desynchronized release in response to a long depolarization was first examined to determine the locus of the effects of FMRFamide. The number of postsynaptic currents during the stimulus was reduced which is consistent with a presynaptic locus of action;The effect of FMRFamide of the presynaptic calcium current was examined since calcium is the trigger for neurotransmitter release. Using voltage clamp techniques, the magnitude of the macroscopic calcium current was found to be reversibly reduced by FMRFamide. There is an additional site of action within the presynaptic terminal. Presynaptic neurons were dialyzed with a photosensitive calcium chelator to elevate and clamp the calcium to a constant level to promote desynchronized release. Under these conditions, secretion from the presynaptic cell was reduced in the presence of FMRFamide. The sensitivity of the secretory machinery to calcium was reduced. Thus, FMRFamide has at least two sites of action in the presynaptic terminal to cause an inhibition of transmitter release;The mechanism of the effect of FMRFamide on the calcium current in growth cones as well as somata was examined further. Using guanine nucleotides and toxins, this inhibitory effect was found to be mediated by a pertussis toxin-sensitive G protein. The inhibitory effect of FMRFamide on action potential-evoked release was also found to be mediated by a pertussis toxin-sensitive G protein. Purified, preactivated [alpha]-subunits of G[subscript] o1, G[subscript] o2, and G[subscript] i3 were microinjected into somata to determine which were able to interact with and inhibit the channels. Of the three G proteins tested, only the [alpha]-subunit of G[subscript] o2 was able to reduce the magnitude of the macroscopic calcium current

Systematic assessment of the quality of osteoporosis guidelines

BACKGROUND: Numerous agencies have developed clinical practice guidelines for the management of postmenopausal osteoporosis. The study objective was to conduct a systematic assessment of the quality of osteoporosis guidelines produced since 1998. METHODS: Guidelines were identified by searching MEDLINE (1998+), the world wide web, known guideline developer websites, bibliographies of retrieved guidelines, and through consultation with content experts. Each guideline was then assessed by three independent appraisers using the 'Appraisal Instrument for Clinical Guidelines' (version 1) by Cluzeau. RESULTS: We identified 26 unique guidelines from 1998–2001 and 21 met our inclusion criteria. Of the 21 guidelines reviewed, 8 were developed by medical societies, 6 by national groups, 6 by government agencies, and 1 by an international group. Twelve of the guidelines were published, 7 were organizational reports, and 2 were accessible only from the web. Half or more of the 20 items assessing the rigor of guideline development were met by 15% (median quality score 23%, range 5–80%, (95% CI 16.5, 34.7)), 81% met at least half of the 12 items assessing guideline content and context (median score 58%, range 17–83%, (95% CI 50.8, 65.5)), and none met half or more of the items assessing guideline application (median score 0%, range 0–47%, (95% CI -0.5 to 12.6)). Eight guidelines described the method used to assess the strength of evidence, and in 6 there was an explicit link between recommendations and the supporting evidence. Ten guidelines were judged not suitable for use in practice, 10 were acceptable with modification, and one was acceptable for use without modification. CONCLUSION: The methodological quality of current osteoporosis guidelines is low, although their scores for clinical content were higher. Virtually no guidelines covered dissemination issues. Few guidelines were judged as acceptable for use in their current format

Feature selection for facial expression recognition

In daily interactions, humans convey their emotions through facial expression and other means. There are several facial expressions that reflect distinctive psychological activities such as happiness, surprise or anger. Accurate recognition of these activities via facial image analysis will play a vital role in natural human-computer interfaces, robotics and mimetic games. This paper focuses on the extraction and selection of salient features for facial expression recognition. We introduce a cascade of fixed filters and trainable non-linear 2-D filters, which are based on the biological mechanism of shunting inhibition. The fixed filters are used to extract primitive features, whereas the adaptive filters are trained to extract more complex facial features for classification by SVMs. This paper investigates a feature selection approach that is based on the reduction of mutual information among the selected features. The proposed approach is evaluated on the JAFFE database with seven types of facial expressions: anger, disgust, fear, happiness, neutral, sadness and surprise. Using only two-thirds of the total features, our approach achieves a classification rate (CR) of 96.7%, which is higher than the CR obtained using all features. Our system also outperforms several existing methods, evaluated on the same JAFFE database

A randomized trial to assess the impact of an antithrombotic decision aid in patients with nonvalvular atrial fibrillation: the DAAFI trial protocol [ISRCTN14429643]

BACKGROUND: Decision aids are often advocated as a means to assist patient and health care provider decision making when faced with complicated treatment or screening decisions. Despite an exponential growth in the availability of decision aids in recent years, their impact on long-term treatment decisions and patient adherence is uncertain due to a paucity of rigorous studies. The choice of antithrombotic therapy for nonvalvular atrial fibrillation (NVAF) is one condition for which a trade-off exists between the potential risks and benefits of competing therapies, and the need to involve patients in decision making has been clearly identified. This study will evaluate whether an evidence-based patient decision aid for patients with NVAF can improve the appropriateness of antithrombotic therapy use by patients and their family physicians. DESIGN: A multi-center, two-armed cluster randomized trial based in community family practices in which patients with NVAF will be randomized to decision aid or usual care. Patients will receive one of four decision aids depending on their baseline stroke risk. The primary outcome is the provision of "appropriate antithrombotic therapy" at 3 months to study participants (appropriateness defined as per the 2001 American College of Chest Physicians recommendations for NVAF). In addition, the impact of this decision aid on patient knowledge, decisional conflict, well-being, and adherence will be assessed after 3 months, 6 months, and 12 months

Patients' perspectives on taking warfarin: qualitative study in family practice

BACKGROUND: Despite the well-documented benefits of using warfarin to prevent stroke, physicians remain reluctant to initiate therapy, and especially so with the elderly owing to the higher risk of hemorrhage. Prior research suggests that patients are more accepting of the risk of bleeding than are physicians, although there have been few qualitative studies. The aim of this study was to employ qualitative methods to investigate the experience and perspective of individuals taking warfarin. METHODS: We conducted face-to-face interviews with 21 older patients (12 male, 9 female) who had been taking warfarin for a minimum of six months. Participants were patients at a family practice clinic situated in a large, tertiary care teaching hospital. We used a semistructured interview guide with four main thematic areas: decision-making, knowledge/education, impact, and satisfaction. Data were analysed according to the principles of content analysis. RESULTS AND DISCUSSION: Participants tended to have minimal input into the decision to initiate warfarin therapy, instead relying in great part on physicians' expertise. There appeared to be low retention of information received regarding the therapy; half the patients in our sample possessed only a superficial level of understanding of the risks and benefits. This notwithstanding, participants reported a high level of satisfaction with the care provided and a low level of impact on their day-to-day lives. CONCLUSIONS: Minimal patient involvement in the initial decision and modest knowledge did not appear to diminish satisfaction with warfarin management. At the same time, care providers exert a tremendous influence on the initiation of warfarin therapy and should strive to incorporate patient preferences and expectations into the decision-making process

Primary care management for optimized antithrombotic treatment [PICANT]: study protocol for a cluster-randomized controlled trial

Background: Antithrombotic treatment is a continuous therapy that is often performed in general practice and requires careful safety management. The aim of this study is to investigate whether a best practice model that applies major elements of case management, including patient education, can improve antithrombotic management in primary health care in terms of reducing major thromboembolic and bleeding events. Methods: This 24-month cluster-randomized trial will be performed in 690 adult patients from 46 practices. The trial intervention will be a complex intervention involving general practitioners, health care assistants and patients with an indication for oral anticoagulation. To assess adherence to medication and symptoms in patients, as well as to detect complications early, health care assistants will be trained in case management and will use the Coagulation-Monitoring-List (Co-MoL) to regularly monitor patients. Patients will receive information (leaflets and a video), treatment monitoring via the Co-MoL and be motivated to perform self-management. Patients in the control group will continue to receive treatment-as-usual from their general practitioners. The primary endpoint is the combined endpoint of all thromboembolic events requiring hospitalization, and all major bleeding complications. Secondary endpoints are mortality, hospitalization, strokes, major bleeding and thromboembolic complications, severe treatment interactions, the number of adverse events, quality of anticoagulation, health-related quality of life and costs. Further secondary objectives will be investigated to explain the mechanism by which the intervention is effective: patients' assessment of chronic illness care, self-reported adherence to medication, general practitioners' and health care assistants' knowledge, patients' knowledge and satisfaction with shared decision making. Practice recruitment is expected to take place between July and December 2012. Recruitment of eligible patients will start in July 2012. Assessment will occur at three time points: baseline (T0), follow-up after 12 (T1) and after 24 months (T2). Discussion: The efficacy and effectiveness of individual elements of the intervention, such as antithrombotic interventions, self-management concepts in orally anticoagulated patients and the methodological tool, case-management, have already been extensively demonstrated. This project foresees the combination of several proven instruments, as a result of which we expect to profit from a reduction in the major complications associated with antithrombotic treatment

Stroke prevention strategies in North American patients with atrial fibrillation:the GLORIA-AF registry program

Thrombosis and Hemostasi

What differences are detected by superiority trials or ruled out by noninferiority trials? A cross-sectional study on a random sample of two-hundred two-arms parallel group randomized clinical trials

BACKGROUND: The smallest difference to be detected in superiority trials or the largest difference to be ruled out in noninferiority trials is a key determinant of sample size, but little guidance exists to help researchers in their choice. The objectives were to examine the distribution of differences that researchers aim to detect in clinical trials and to verify that those differences are smaller in noninferiority compared to superiority trials. METHODS: Cross-sectional study based on a random sample of two hundred two-arm, parallel group superiority (100) and noninferiority (100) randomized clinical trials published between 2004 and 2009 in 27 leading medical journals. The main outcome measure was the smallest difference in favor of the new treatment to be detected (superiority trials) or largest unfavorable difference to be ruled out (noninferiority trials) used for sample size computation, expressed as standardized difference in proportions, or standardized difference in means. Student t test and analysis of variance were used. RESULTS: The differences to be detected or ruled out varied considerably from one study to the next; e.g., for superiority trials, the standardized difference in means ranged from 0.007 to 0.87, and the standardized difference in proportions from 0.04 to 1.56. On average, superiority trials were designed to detect larger differences than noninferiority trials (standardized difference in proportions: mean 0.37 versus 0.27, P = 0.001; standardized difference in means: 0.56 versus 0.40, P = 0.006). Standardized differences were lower for mortality than for other outcomes, and lower in cardiovascular trials than in other research areas. CONCLUSIONS: Superiority trials are designed to detect larger differences than noninferiority trials are designed to rule out. The variability between studies is considerable and is partly explained by the type of outcome and the medical context. A more explicit and rational approach to choosing the difference to be detected or to be ruled out in clinical trials may be desirable

What differences are detected by superiority trials or ruled out by noninferiority trials? A cross-sectional study on a random sample of two-hundred two-arms parallel group randomized clinical trials

<p>Abstract</p> <p>Background</p> <p>The smallest difference to be detected in superiority trials or the largest difference to be ruled out in noninferiority trials is a key determinant of sample size, but little guidance exists to help researchers in their choice. The objectives were to examine the distribution of differences that researchers aim to detect in clinical trials and to verify that those differences are smaller in noninferiority compared to superiority trials.</p> <p>Methods</p> <p>Cross-sectional study based on a random sample of two hundred two-arm, parallel group superiority (100) and noninferiority (100) randomized clinical trials published between 2004 and 2009 in 27 leading medical journals. The main outcome measure was the smallest difference in favor of the new treatment to be detected (superiority trials) or largest unfavorable difference to be ruled out (noninferiority trials) used for sample size computation, expressed as standardized difference in proportions, or standardized difference in means. Student t test and analysis of variance were used.</p> <p>Results</p> <p>The differences to be detected or ruled out varied considerably from one study to the next; e.g., for superiority trials, the standardized difference in means ranged from 0.007 to 0.87, and the standardized difference in proportions from 0.04 to 1.56. On average, superiority trials were designed to detect larger differences than noninferiority trials (standardized difference in proportions: mean 0.37 versus 0.27, <it>P </it>= 0.001; standardized difference in means: 0.56 versus 0.40, <it>P </it>= 0.006). Standardized differences were lower for mortality than for other outcomes, and lower in cardiovascular trials than in other research areas.</p> <p>Conclusions</p> <p>Superiority trials are designed to detect larger differences than noninferiority trials are designed to rule out. The variability between studies is considerable and is partly explained by the type of outcome and the medical context. A more explicit and rational approach to choosing the difference to be detected or to be ruled out in clinical trials may be desirable.</p