Neurally adjusted ventilatory assist in patients with critical illness-associated polyneuromyopathy

Diaphragmatic electrical activity (EA(di)), reflecting respiratory drive, and its feedback control might be impaired in critical illness-associated polyneuromyopathy (CIPM). We aimed to evaluate whether titration and prolonged application of neurally adjusted ventilatory assist (NAVA), which delivers pressure (P (aw)) in proportion to EA(di), is feasible in CIPM patients.

A robust reference signal generator for synchronized ventricular assist devices

Ventricular assist devices (VADs) are blood pumps that offer an option to support the circulation of patients with severe heart failure. Since a failing heart has a remaining pump function, its interaction with the VAD influences the hemodynamics. Ideally, the heart's action is taken into account for actuating the device such that the device is synchronized to the natural cardiac cycle. To realize this in practice, a reliable real-time algorithm for the automatic synchronization of the VAD to the heart rate is required. This paper defines the tasks such an algorithm needs to fulfill: the automatic detection of irregular heart beats and the feedback control of the phase shift between the systolic phases of the heart and the assist device. We demonstrate a possible solution to these problems and analyze its performance in two steps. First, the algorithm is tested using the MIT-BIH arrhythmia database. Second, the algorithm is implemented in a controller for a pulsatile and a continuous-flow VAD. These devices are connected to a hybrid mock circulation where three test scenarios are evaluated. The proposed algorithm ensures a reliable synchronization of the VAD to the heart cycle, while being insensitive to irregularities in the heart rate.

Control of muscle relaxation during anesthesia: a novel approach for clinical routine

During general anesthesia drugs are administered to provide hypnosis, ensure analgesia, and skeletal muscle relaxation. In this paper, the main components of a newly developed controller for skeletal muscle relaxation are described. Muscle relaxation is controlled by administration of neuromuscular blocking agents. The degree of relaxation is assessed by supramaximal train-of-four stimulation of the ulnar nerve and measuring the electromyogram response of the adductor pollicis muscle. For closed-loop control purposes, a physiologically based pharmacokinetic and pharmacodynamic model of the neuromuscular blocking agent mivacurium is derived. The model is used to design an observer-based state feedback controller. Contrary to similar automatic systems described in the literature this controller makes use of two different measures obtained in the train-of-four measurement to maintain the desired level of relaxation. The controller is validated in a clinical study comparing the performance of the controller to the performance of the anesthesiologist. As presented, the controller was able to maintain a preselected degree of muscle relaxation with excellent precision while minimizing drug administration. The controller performed at least equally well as the anesthesiologist.

Reliability of intraoperative high-resolution 2D ultrasound as an alternative to high-field strength MR imaging for tumor resection control: a prospective comparative study

OBJECT: Ultrasound may be a reliable but simpler alternative to intraoperative MR imaging (iMR imaging) for tumor resection control. However, its reliability in the detection of tumor remnants has not been definitely proven. The aim of the study was to compare high-field iMR imaging (1.5 T) and high-resolution 2D ultrasound in terms of tumor resection control. METHODS: A prospective comparative study of 26 consecutive patients was performed. The following parameters were compared: the existence of tumor remnants after presumed radical removal and the quality of the images. Tumor remnants were categorized as: detectable with both imaging modalities or visible only with 1 modality. RESULTS: Tumor remnants were detected in 21 cases (80.8%) with iMR imaging. All large remnants were demonstrated with both modalities, and their image quality was good. Two-dimensional ultrasound was not as effective in detecting remnants<1 cm. Two remnants detected with iMR imaging were missed by ultrasound. In 2 cases suspicious signals visible only on ultrasound images were misinterpreted as remnants but turned out to be a blood clot and peritumoral parenchyma. The average time for acquisition of an ultrasound image was 2 minutes, whereas that for an iMR image was approximately 10 minutes. Neither modality resulted in any procedure-related complications or morbidity. CONCLUSIONS: Intraoperative MR imaging is more precise in detecting small tumor remnants than 2D ultrasound. Nevertheless, the latter may be used as a less expensive and less time-consuming alternative that provides almost real-time feedback information. Its accuracy is highest in case of more confined, deeply located remnants. In cases of more superficially located remnants, its role is more limited.

Impacts of a word-picture training on reading in youth with mixed intellectual disabilities. A waiting-list control group comparison

Individuals with intellectual disabilities (ID) often struggle with learning how to read. Reading difficulties seem to be the most common secondary condition of ID. Only one in five children with mild or moderate ID achieves even minimal literacy skills. However, literacy education for children and adolescents with ID has been largely overlooked by researchers and educators. While there is little research on reading of children with ID, many training studies have been conducted with other populations with reading difficulties. The most common approach of acquiring literacy skills consists of sophisticated programs that train phonological skills and auditory perception. Only few studies investigated the influence of implicit learning on literacy skills. Implicit learning processes seem to be largely independent of age and IQ. Children are sensitive to the statistics of their learning environment. By frequent word reading they acquire implicit knowledge about the frequency of single letters and letter patterns in written words. Additionally, semantic connections not only improve the word understanding, but also facilitate storage of words in memory. Advances in communication technology have introduced new possibilities for remediating literacy skills. Computers can provide training material in attractive ways, for example through animations and immediate feedback .These opportunities can scaffold and support attention processes central to learning. Thus, the aim of this intervention study was to develop and implement a computer based word-picture training, which is based on statistical and semantic learning, and to examine the training effects on reading, spelling and attention in children and adolescents (9-16 years) diagnosed with mental retardation (general IQ  74). Fifty children participated in four to five weekly training sessions of 15-20 minutes over 4 weeks, and completed assessments of attention, reading, spelling, short-term memory and fluid intelligence before and after training. After a first assessment (T1), the entire sample was divided in a training group (group A) and a waiting control group (group B). After 4 weeks of training with group A, a second assessment (T2) was administered with both training groups. Afterwards, group B was trained for 4 weeks, before a last assessment (T3) was carried out in both groups. Overall, the results showed that the word-picture training led to substantial gains on word decoding and attention for both training groups. These effects were preserved six weeks later (group A). There was also a clear tendency of improvement in spelling after training for both groups, although the effect did not reach significance. These findings highlight the fact that an implicit statistical learning training in a playful way by motivating computer programs can not only promote reading development, but also attention in children with intellectual disabilities.

Quality Control for SP Performance Regarding Patient Portrayal in a High-Stakes OSCE

Introduction Since the quality of patient portrayal of standardized patients (SPs) during an Objective Structured Clinical Exam (OSCE) has a major impact on the reliability and validity of the exam, quality control should be initiated. Literature about quality control of SP’s performance focuses on feedback [1, 2] or completion of checklists [3, 4]. Since we did not find a published instrument meeting our needs for the assessment of patient portrayal, we developed such an instrument after being inspired by others [5] and used it in our high-stakes exam. Methods SP trainers from all five Swiss medical faculties collected and prioritized quality criteria for patient portrayal. Items were revised with the partners twice, based on experiences during OSCEs. The final instrument contains 14 criteria for acting (i.e. adequate verbal and non-verbal expression) and standardization (i.e. verbatim delivery of the first sentence). All partners used the instrument during a high-stakes OSCE. Both, SPs and trainers were introduced to the instrument. The tool was used in training (more than 100 observations) and during the exam (more than 250 observations). FAIR_OSCE The list of items to assess the quality of the simulation by SPs was primarily developed and used to provide formative feedback to the SPs in order to help them to improve their performance. It was therefore named “Feedbackstruckture for the Assessment of Interactive Role play in Objective Structured Clinical Exams (FAIR_OSCE). It was also used to assess the quality of patient portrayal during the exam. The results were calculated for each of the five faculties individually. Formative evaluation was given to the five faculties with individual feedback without revealing results of other faculties other than overall results. Results High quality of patient portrayal during the exam was documented. More than 90% of SP performances were rated to be completely correct or sufficient. An increase in quality of performance between training and exam was noted. In example the rate of completely correct reaction in medical tests increased from 88% to 95%. 95% completely correct reactions together with 4% sufficient reactions add up to 99% of the reactions meeting the requirements of the exam. SP educators using the instrument reported an augmentation of SPs performance induced by the use of the instrument. Disadvantages mentioned were high concentration needed to explicitly observe all criteria and cumbersome handling of the paper-based forms. Conclusion We were able to document a very high quality of SP performance in our exam. The data also indicate that our training is effective. We believe that the high concentration needed using the instrument is well invested, considering the observed augmentation of performance. The development of an iPad based application for the form is planned to address the cumbersome handling of the paper.

FAIR_OSCE – Feedback structure for assessment of interactive roleplay in Objective Structured Clinical Exams

Introduction Since the quality of patient portrayal of standardized patients (SPs) during an Objective Structured Clinical Exam (OSCE) has a major impact on the reliability and validity of the exam, quality control should be initiated. Literature about quality control of SPs’ performance focuses on feedback [1, 2] or completion of checklists [3, 4]. Since we did not find a published instrument meeting our needs for the assessment of patient portrayal, we developed such an instrument after being inspired by others [5] and used it in our high-stakes exam. Project description SP trainers from five medical faculties collected and prioritized quality criteria for patient portrayal. Items were revised twice, based on experiences during OSCEs. The final instrument contains 14 criteria for acting (i.e. adequate verbal and non-verbal expression) and standardization (i.e. verbatim delivery of the first sentence). All partners used the instrument during a high-stakes OSCE. SPs and trainers were introduced to the instrument. The tool was used in training (more than 100 observations) and during the exam (more than 250 observations). Outcome High quality of SPs’ patient portrayal during the exam was documented. More than 90% of SP performances were rated to be completely correct or sufficient. An increase in quality of performance between training and exam was noted. For example, the rate of completely correct reaction in medical tests increased from 88% to 95%. Together with 4% of sufficient performances these 95% add up to 99% of the reactions in medical tests meeting the standards of the exam. SP educators using the instrument reported an augmentation of SPs’ performance induced by the use of the instrument. Disadvantages mentioned were the high concentration needed to observe all criteria and the cumbersome handling of the paper-based forms. Discussion We were able to document a very high quality of SP performance in our exam. The data also indicates that our training is effective. We believe that the high concentration needed using the instrument is well invested, considering the observed enhancement of performance. The development of an iPad-based application for the form is planned to address the cumbersome handling of the paper.

Quality assurance of simulated patient feedback in communication training for fourth-year medical students

Introduction In our program, simulated patients (SPs) give feedback to medical students in the course of communication skills training. To ensure effective training, quality control of the SPs’ feedback should be implemented. At other institutions, medical students evaluate the SPs’ feedback for quality control (Bouter et al., 2012). Thinking about implementing quality control for SPs’ feedback in our program, we wondered whether the evaluation by students would result in the same scores as evaluation by experts. Methods Consultations simulated by 4th-year medical students with SPs were video taped including the SP’s feedback to the students (n=85). At the end of the training sessions students rated the SPs’ performance using a rating instrument called Bernese Assessment for Role-play and Feedback (BARF) containing 11 items concerning feedback quality. Additionally the videos were evaluated by 3 trained experts using the BARF. Results The experts showed a high interrater agreement when rating identical feedbacks (ICCunjust=0.953). Comparing the rating of students and experts, high agreement was found with regard to the following items: 1. The SP invited the student to reflect on the consultation first, Amin (= minimal agreement) 97% 2. The SP asked the student what he/she liked about the consultation, Amin = 88%. 3. The SP started with positive feedback, Amin = 91%. 4. The SP was comparing the student with other students, Amin = 92%. In contrast the following items showed differences between the rating of experts and students: 1. The SP used precise situations for feedback, Amax (=maximal agreement) 55%, Students rated 67 of SPs’ feedbacks to be perfect with regard to this item (highest rating on a 5 point Likert scale), while only 29 feedbacks were rated this way by the experts. 2. The SP gave precise suggestions for improvement, Amax 75%, 62 of SPs’ feedbacks obtained the highest rating from students, while only 44 of SPs’ feedbacks achieved the highest rating in the view of the experts. 3. The SP speaks about his/her role in the third person, Amax 60%. Students rated 77 feedbacks with the highest score, while experts judged only 43 feedbacks this way. Conclusion Although evaluation by the students was in agreement with that of experts concerning some items, students rated the SPs’ feedback more often with the optimal score than experts did. Moreover it seems difficult for students to notice when SPs talk about the role in the first instead of the third person. Since precision and talking about the role in the third person are important quality criteria of feedback, this result should be taken into account when thinking about students’ evaluation of SPs’ feedback for quality control. Bouter, S., E. van Weel-Baumgarten, and S. Bolhuis. 2012. Construction and Validation of the Nijmegen Evaluation of the Simulated Patient (NESP): Assessing Simulated Patients’ Ability to Role-Play and Provide Feedback to Students. Academic Medicine: Journal of the Association of American Medical Colleges

Functional lateralization of the anterior insula during feedback processing

Effective adaptive behavior rests on an appropriate understanding of how much responsibility we have over outcomes in the environment. This attribution of agency to ourselves or to an external event influences our behavioral and affective response to the outcomes. Despite its special importance to understanding human motivation and affect, the neural mechanisms involved in self-attributed rewards and punishments remain unclear. Previous evidence implicates the anterior insula (AI) in evaluating the consequences of our own actions. However, it is unclear if the AI has a general role in feedback evaluation (positive and negative) or plays a specific role during error processing. Using functional magnetic resonance imaging and a motion prediction task, we investigate neural responses to self- and externally attributed monetary gains and losses. We found that attribution effects vary according to the valence of feedback: significant valence × attribution interactions in the right AI, the anterior cingulate cortex (ACC), the midbrain, and the right ventral putamen. Self-attributed losses were associated with increased activity in the midbrain, the ACC and the right AI, and negative BOLD response in the ventral putamen. However, higher BOLD activity to self-attributed feedback (losses and gains) was observed in the left AI, the thalamus, and the cerebellar vermis. These results suggest a functional lateralization of the AI. The right AI, together with the midbrain and the ACC, is mainly involved in processing the salience of the outcome, whereas the left is part of a cerebello-thalamic-cortical pathway involved in cognitive control processes important for subsequent behavioral adaptations.

The H19/let-7 double-negative feedback loop contributes to glucose metabolism in muscle cells

The H19 lncRNA has been implicated in development and growth control and is associated with human genetic disorders and cancer. Acting as a molecular sponge, H19 inhibits microRNA (miRNA) let-7. Here we report that H19 is significantly decreased in muscle of human subjects with type-2 diabetes and insulin resistant rodents. This decrease leads to increased bioavailability of let-7, causing diminished expression of let-7 targets, which is recapitulated in vitro where H19 depletion results in impaired insulin signaling and decreased glucose uptake. Furthermore, acute hyperinsulinemia downregulates H19, a phenomenon that occurs through PI3K/AKT-dependent phosphorylation of the miRNA processing factor KSRP, which promotes biogenesis of let-7 and its mediated H19 destabilization. Our results reveal a previously undescribed double-negative feedback loop between sponge lncRNA and target miRNA that contributes to glucose regulation in muscle cells.

Valence and agency influence striatal response to feedback in patients with major depressive disorder

BACKGROUND: Reduced sensitivity to positive feedback is common in patients with major depressive disorder (MDD). However, findings regarding negative feedback are ambiguous, with both exaggerated and blunted responses being reported. The ventral striatum (VS) plays a major role in processing valenced feedback, and previous imaging studies have shown that the locus of controls (self agency v. external agency) over the outcome influences VS response to feedback. We investigated whether attributing the outcome to one's own action or to an external agent influences feedback processing in patients with MDD. We hypothesized that depressed participants would be less sensitive to the feedback attribution reflected by an altered VS response to self-attributed gains and losses. METHODS: Using functional MRI and a motion prediction task, we investigated the neural responses to self-attributed (SA) and externally attributed (EA) monetary gains and losses in unmedicated patients with MDD and healthy controls. RESULTS: We included 21 patients and 25 controls in our study. Consistent with our prediction, healthy controls showed a VS response influenced by feedback valence and attribution, whereas in depressed patients striatal activity was modulated by valence but was insensitive to attribution. This attribution insensitivity led to an altered ventral putamen response for SA - EA losses in patients with MDD compared with healthy controls. LIMITATIONS: Depressed patients with comorbid anxiety disorder were included. CONCLUSION: These results suggest an altered assignment of motivational salience to SA losses in patients with MDD. Altered striatal response to SA negative events may reinforce the belief of not being in control of negative outcomes contributing to a cycle of learned helplessness.

The Rice Transcription Factor WRKY53 Suppresses Herbivore-Induced Defenses by Acting as a Negative Feedback Modulator of Mitogen-Activated Protein Kinase Activity

The mechanisms by which herbivore-attacked plants activate their defenses are well studied. By contrast, little is known about the regulatory mechanisms that allow them to control their defensive investment and avoid a defensive overshoot. We characterized a rice (Oryza sativa) WRKY gene, OsWRKY53, whose expression is rapidly induced upon wounding and induced in a delayed fashion upon attack by the striped stem borer (SSB) Chilo suppressalis. The transcript levels of OsWRKY53 are independent of endogenous jasmonic acid but positively regulated by the mitogen-activated protein kinases OsMPK3/OsMPK6. OsWRKY53 physically interacts with OsMPK3/OsMPK6 and suppresses their activity in vitro. By consequence, it modulates the expression of defensive, MPK-regulated WRKYs and thereby reduces jasmonic acid, jasmonoyl-isoleucine, and ethylene induction. This phytohormonal reconfiguration is associated with a reduction in trypsin protease inhibitor activity and improved SSB performance. OsWRKY53 is also shown to be a negative regulator of plant growth. Taken together, these results show that OsWRKY53 functions as a negative feedback modulator of MPK3/MPK6 and thereby acts as an early suppressor of induced defenses. OsWRKY53 therefore enables rice plants to control the magnitude of their defensive investment during early signaling.

Sustained impact of a short small group course with systematic feedback in addition to regular clinical clerkship activities on musculoskeletal examination skills-a controlled study.

BACKGROUND The discrepancy between the extensive impact of musculoskeletal complaints and the common deficiencies in musculoskeletal examination skills lead to increased emphasis on structured teaching and assessment. However, studies of single interventions are scarce and little is known about the time-dependent effect of assisted learning in addition to a standard curriculum. We therefore evaluated the immediate and long-term impact of a small group course on musculoskeletal examination skills. METHODS All 48 Year 4 medical students of a 6 year curriculum, attending their 8 week clerkship of internal medicine at one University department in Berne, participated in this controlled study. Twenty-seven students were assigned to the intervention of a 6×1 h practical course (4-7 students, interactive hands-on examination of real patients; systematic, detailed feedback to each student by teacher, peers and patients). Twenty-one students took part in the regular clerkship activities only and served as controls. In all students clinical skills (CS, 9 items) were assessed in an Objective Structured Clinical Examination (OSCE) station, including specific musculoskeletal examination skills (MSES, 7 items) and interpersonal skills (IPS, 2 items). Two raters assessed the skills on a 4-point Likert scale at the beginning (T0), the end (T1) and 4-12 months after (T2) the clerkship. Statistical analyses included Friedman test, Wilcoxon rank sum test and Mann-Whitney U test. RESULTS At T0 there were no significant differences between the intervention and control group. At T1 and T2 the control group showed no significant changes of CS, MSES and IPS compared to T0. In contrast, the intervention group significantly improved CS, MSES and IPS at T1 (p < 0.001). This enhancement was sustained for CS and MSES (p < 0.05), but not for IPS at T2. CONCLUSIONS Year 4 medical students were incapable of improving their musculoskeletal examination skills during regular clinical clerkship activities. However, an additional small group, interactive clinical skills course with feedback from various sources, improved these essential examination skills immediately after the teaching and several months later. We conclude that supplementary specific teaching activities are needed. Even a single, short-lasting targeted module can have a long lasting effect and is worth the additional effort.

Short structured feedback training is equivalent to a mechanical feedback device in two-rescuer BLS: a randomised simulation study.

BACKGROUND Resuscitation guidelines encourage the use of cardiopulmonary resuscitation (CPR) feedback devices implying better outcomes after sudden cardiac arrest. Whether effective continuous feedback could also be given verbally by a second rescuer ("human feedback") has not been investigated yet. We, therefore, compared the effect of human feedback to a CPR feedback device. METHODS In an open, prospective, randomised, controlled trial, we compared CPR performance of three groups of medical students in a two-rescuer scenario. Group "sCPR" was taught standard BLS without continuous feedback, serving as control. Group "mfCPR" was taught BLS with mechanical audio-visual feedback (HeartStart MRx with Q-CPR-Technology™). Group "hfCPR" was taught standard BLS with human feedback. Afterwards, 326 medical students performed two-rescuer BLS on a manikin for 8 min. CPR quality parameters, such as "effective compression ratio" (ECR: compressions with correct hand position, depth and complete decompression multiplied by flow-time fraction), and other compression, ventilation and time-related parameters were assessed for all groups. RESULTS ECR was comparable between the hfCPR and the mfCPR group (0.33 vs. 0.35, p = 0.435). The hfCPR group needed less time until starting chest compressions (2 vs. 8 s, p < 0.001) and showed fewer incorrect decompressions (26 vs. 33 %, p = 0.044). On the other hand, absolute hands-off time was higher in the hfCPR group (67 vs. 60 s, p = 0.021). CONCLUSIONS The quality of CPR with human feedback or by using a mechanical audio-visual feedback device was similar. Further studies should investigate whether extended human feedback training could further increase CPR quality at comparable costs for training.