Repetitive vascular occlusion stimulus (RVOS) versus standard care to prevent muscle wasting in critically ill patients (ROSProx):a study protocol for a pilot randomised controlled trial

Background Forty per cent of critically ill patients are affected by intensive care unit-acquired weakness (ICU-AW), to which skeletal muscle wasting makes a substantial contribution. This can impair outcomes in hospital, and can cause long-term physical disability after hospital discharge. No effective mitigating strategies have yet been identified. Application of a repetitive vascular occlusion stimulus (RVOS) a limb pressure cuff inducing brief repeated cycles of ischaemia and reperfusion, can limit disuse muscle atrophy in both healthy controls and bed-bound patients recovering from knee surgery. We wish to determine whether RVOS might be effective in mitigating against muscle wasting in the ICU. Given that RVOS can also improve vascular function in healthy controls, we also wish to assess such effects in the critically ill. We here describe a pilot study to assess whether RVOS application is safe, tolerable, feasible and acceptable for ICU patients. Methods This is a randomised interventional feasibility trial. Thirty-two ventilated adult ICU patients with multiorgan failure will be recruited within 48 h of admission and randomised to either the intervention arm or the control arm. Intervention participants will receive RVOS twice daily (except only once on day 1) for up to 10 days or until ICU discharge. Serious adverse events and tolerability (pain score) will be recorded; feasibility of trial procedures will be assessed against pre-specified criteria and acceptability by semi-structured interview. Together with vascular function, muscle mass and quality will be assessed using ultrasound and measures of physical function at baseline, on days 6 and 11 of study enrolment, and at ICU and hospital discharge. Blood and urine biomarkers of muscle metabolism, vascular function, inflammation and DNA damage/repair mechanism will also be analysed. The Health questionnaire will be completed 3 months after hospital discharge. Discussion If this study demonstrates feasibility, the derived data will be used to inform the design (and sample size) of an appropriately-powered prospective trial to clarify whether RVOS can help preserve muscle mass/improve vascular function in critically ill patients.</p

Students’ Self-Perceptions of Self-Awareness/Self-Regulation when Experiencing Unexpected Situations in an Interprofessional Clinical Simulation

Background: The healthcare environment is becoming increasingly complex and demanding; therefore, providers need to possess both technical and non-technical skills to respond in unexpected circumstances. Self-awareness and regulation are non-technical skills where an individual becomes aware of personal and others’ emotions and then modulates those emotions to effectively act during a challenging situation. Educational programs need to embed more opportunities for students to develop these skills to enhance patient outcomes. Purpose: The purpose of this research study was to explore student self-perceptions of self-awareness and self-regulation when experiencing unexpected situations in an interprofessional clinical simulation. Methods: Healthcare students (n = 109) from four disciplines participated in this qualitative research study involving an interprofessional small group, face to face simulation with unexpected circumstances. Following the simulation, participants engaged in a semi-structured debriefing. Comments were recorded and analyzed to develop a thematic structure. Results: Participants had varying views about their level of preparedness to handle complex, unexpected situations ranging from feeling not prepared at all to recognizing that they need to be equipped for anything. Students also reported a greater appreciation for the interprofessional team, acknowledging the need for one another as they navigated unexpected circumstances. Some students used their self-awareness and regulation skills in the moment to manage their emotions and move to action in response to the unexpected circumstances, while others benefited from observing and hearing from others during the simulation and debriefing session. Conclusions: The interprofessional simulation helped to prepare students to navigate unexpected challenging patient care circumstances. Students experienced some role and action confusion in response to the emotionally charged scenario; however, they recognized the importance of being self-aware, regulating their own emotions and the skills of the interdisciplinary team to best meet the needs of the patient and family. Additional opportunities for non-technical skill practice should be included in healthcare curriculums to enhance students’ preparedness for the current healthcare environment. Further research is recommended to determine best practices for teaching these non-technical skills

Teaching clinical informatics to third-year medical students: negative results from two controlled trials

BACKGROUND: Prior educational interventions to increase seeking evidence by medical students have been unsuccessful. METHODS: We report two quasirandomized controlled trials to increase seeking of medical evidence by third-year medical students. In the first trial (1997–1998), we placed computers in clinical locations and taught their use in a 6-hour course. Based on negative results, we created SUMSearch(TM), an Internet site that automates searching for medical evidence by simultaneous meta-searching of MEDLINE and other sites. In the second trial (1999–2000), we taught SUMSearch's use in a 5½-hour course. Both courses were taught during the medicine clerkship. For each trial, we surveyed the entire third-year class at 6 months, after half of the students had taken the course (intervention group). The students who had not received the intervention were the control group. We measured self-report of search frequency and satisfaction with search quality and speed. RESULTS: The proportion of all students who reported searching at least weekly for medical evidence significantly increased from 19% (1997–1998) to 42% (1999–2000). The proportion of all students who were satisfied with their search results increased significantly between study years. However, in neither study year did the interventions increase searching or satisfaction with results. Satisfaction with the speed of searching was 27% in 1999–2000. This did not increase between studies years and was not changed by the interventions. CONCLUSION: None of our interventions affected searching habits. Even with automated searching, students report low satisfaction with search speed. We are concerned that students using current strategies for seeking medical evidence will be less likely to seek and appraise original studies when they enter medical practice and have less time

Targeted Disruption of the Low-Affinity Leukemia Inhibitory Factor-Receptor Gene Causes Placental, Skeletal, Neural and Metabolic Defects and Results in Perinatal Death

The low-affinity receptor for leukemia inhibitory factor (LIFR)* interacts with gp130 to induce an intracellular signal cascade, The LIFR-gp130 heterodimer is implicated in the function of diverse systems, Normal placentation is disrupted in LIFR mutant animals, which leads to poor intrauterine nutrition but allows fetuses to continue to term. Fetal bone volume is reduced greater than three-fold and the number of osteoclasts is increased six-fold, resulting in severe osteopenia of perinatal bone. Astrocyte numbers are reduced in the spinal cord and brain stem. Late gestation fetal livers contain relatively high stores of glycogen, indicating a metabolic disorder. Hematologic and primordial germ cell compartments appear normal. Pleiotropic defects in the mutant animals preclude survival beyond the day of birth

Incubation of ovine scrapie with environmental matrix results in biological and biochemical changes of PrPSc over time

Ovine scrapie can be transmitted via environmental reservoirs. A pool of ovine scrapie isolates were incubated on soil for one day or thirteen months and eluted prion was used to challenge tg338 mice transgenic for ovine PrP. After one-day incubation on soil, two PrPSc phenotypes were present: G338 or Apl338ii. Thirteen months later some divergent PrPSc phenotypes were seen: a mixture of Apl338ii with either G338 or P338, and a completely novel PrPSc deposition, designated Cag338. The data show that prolonged ageing of scrapie prions within an environmental matrix may result in changes in the dominant PrPSc biological/biochemical properties

Testing the paradox of enrichment along a land use gradient in a multitrophic aboveground and belowground community

In the light of ongoing land use changes, it is important to understand how multitrophic communities perform at different land use intensities. The paradox of enrichment predicts that fertilization leads to destabilization and extinction of predator-prey systems. We tested this prediction for a land use intensity gradient from natural to highly fertilized agricultural ecosystems. We included multiple aboveground and belowground trophic levels and land use-dependent searching efficiencies of insects. To overcome logistic constraints of field experiments, we used a successfully validated simulation model to investigate plant responses to removal of herbivores and their enemies. Consistent with our predictions, instability measured by herbivore-induced plant mortality increased with increasing land use intensity. Simultaneously, the balance between herbivores and natural enemies turned increasingly towards herbivore dominance and natural enemy failure. Under natural conditions, there were more frequently significant effects of belowground herbivores and their natural enemies on plant performance, whereas there were more aboveground effects in agroecosystems. This result was partly due to the “boom-bust” behavior of the shoot herbivore population. Plant responses to herbivore or natural enemy removal were much more abrupt than the imposed smooth land use intensity gradient. This may be due to the presence of multiple trophic levels aboveground and belowground. Our model suggests that destabilization and extinction are more likely to occur in agroecosystems than in natural communities, but the shape of the relationship is nonlinear under the influence of multiple trophic interactions.

A Computational Approach to Understand In Vitro Alveolar Morphogenesis

Primary human alveolar type II (AT II) epithelial cells maintained in Matrigel cultures form alveolar-like cysts (ALCs) using a cytogenesis mechanism that is different from that of other studied epithelial cell types: neither proliferation nor death is involved. During ALC formation, AT II cells engage simultaneously in fundamentally different, but not fully characterized activities. Mechanisms enabling these activities and the roles they play during different process stages are virtually unknown. Identifying, characterizing, and understanding the activities and mechanisms are essential to achieving deeper insight into this fundamental feature of morphogenesis. That deeper insight is needed to answer important questions. When and how does an AT cell choose to switch from one activity to another? Why does it choose one action rather than another? We report obtaining plausible answers using a rigorous, multi-attribute modeling and simulation approach that leveraged earlier efforts by using new, agent and object-oriented capabilities. We discovered a set of cell-level operating principles that enabled in silico cells to self-organize and generate systemic cystogenesis phenomena that are quantitatively indistinguishable from those observed in vitro. Success required that the cell components be quasi-autonomous. As simulation time advances, each in silico cell autonomously updates its environment information to reclassify its condition. It then uses the axiomatic operating principles to execute just one action for each possible condition. The quasi-autonomous actions of individual in silico cells were sufficient for developing stable cyst-like structures. The results strengthen in silico to in vitro mappings at three levels: mechanisms, behaviors, and operating principles, thereby achieving a degree of validation and enabling answering the questions posed. We suggest that the in silico operating principles presented may have a biological counterpart and that a semiquantitative mapping exists between in silico causal events and in vitro causal events

Fusion of Color Doppler and Magnetic Resonance Images of the Heart

This study was designed to establish and analyze color Doppler and magnetic resonance fusion images of the heart, an approach for simultaneous testing of cardiac pathological alterations, performance, and hemodynamics. Ten volunteers were tested in this study. The echocardiographic images were produced by Philips IE33 system and the magnetic resonance images were generated from Philips 3.0-T system. The fusion application was implemented on MATLAB platform utilizing image processing technology. The fusion image was generated from the following steps: (1) color Doppler blood flow segmentation, (2) image registration of color Doppler and magnetic resonance imaging, and (3) image fusion of different image types. The fusion images of color Doppler blood flow and magnetic resonance images were implemented by MATLAB programming in our laboratory. Images and videos were displayed and saved as AVI and JPG. The present study shows that the method we have developed can be used to fuse color flow Doppler and magnetic resonance images of the heart. We believe that the method has the potential to: fill in information missing from the ultrasound or MRI alone, show structures outside the field of view of the ultrasound through MR imaging, and obtain complementary information through the fusion of the two imaging methods (structure from MRI and function from ultrasound)