Effectiveness of a virtual reality trainer for retention of tourniquet application skills for hemorrhage control among emergency medicine residents.

Background: With a rise in mass casualty incidents, training in hemorrhage control using tourniquets has been championed as a basic-and lifesaving-procedure for bystanders and medical professionals alike. The current standard for training is in-person (IP) courses, which can be limited based on instructor availability. Virtual reality (VR) has demonstrated the potential to improve the accuracy of certain medical tasks but has not yet been developed for hemorrhage control. The objective of this study was to evaluate the efficacy of a VR hemorrhage trainer in learner retention of tourniquet application when compared to traditional IP instructor teaching among a cohort of emergency medicine residents practicing in a Level I trauma center. Methods: This was a prospective, observational study of 53 emergency medicine residents at an inner-city program. Participants were randomly assigned to either the control or the VR group. On Day 0, all residents underwent a training session (IP vs. VR) for the proper, stepwise application of a tourniquet, as defined by the American College of Trauma Surgeons. Each participant was then assessed on the application of a tourniquet by a blinded instructor using the National Registry Hemorrhage Control Skills Lab rubric. After 3 months, each resident was reevaluated on the same rubric, with subsequent data analysis on successful tourniquet placement (measured as under 90 s) and time to completion. Results: Of the 53 participants, the IP training group had an initial pass rate of 97% (28/29) compared to 92% (22/24) in the VR group (p = 0.58). On retention testing, the IP training group had a pass rate of 95% (20/21) compared to 90% (18/20) in the VR group (p = 0.62). Stratifying the success of tourniquet placement by level of resident training did not demonstrate any statistically significant differences. Conclusions: In this pilot study of emergency medicine residents, we found no significant differences in successful hemorrhage control by tourniquet placement between those trained with VR compared to a traditional IP course among emergency medicine residents. While more studies with greater power are needed, the results suggest that VR may be a useful adjunct to traditional IP medical training.

Infant hydrocephalus in sub-Saharan Africa: the reality on the Tanzanian side of the lake.

OBJECTIVE Infant hydrocephalus is estimated to affect more than 100,000 new infants each year in sub-Saharan Africa (SSA). Bugando Medical Centre (BMC), a government-funded and patient cost-shared referral center, serves over 13 million people in the Lake and Western regions of Tanzania. The goals of this study were to characterize the infant population affected by hydrocephalus who presented to BMC and were treated with a ventriculoperitoneal shunt (VPS) to determine the rate of early complications associated with this surgical procedure and to assess its potential risk factors. METHODS Data were prospectively collected from all patients less than 1 year of age who, over a period of 7 months, were diagnosed with hydrocephalus and admitted to BMC for insertion of a primary VPS. Demographic data, maternal history, preoperative studies, surgical procedure, and surgical complications developing by the time of the first follow-up visit were analyzed. Risk factors associated with the surgical complications were determined. RESULTS During the 7-month study period, 125 infants eligible for the study were included in the analysis. Overall, 75% were younger than 6 months of age, and 56% were males. Only 7% of mothers had a gestational ultrasound, 98% did not receive preconception folic acid, and 25% delivered their child at home. In most patients with hydrocephalus the etiology was uncertain (56%), and other patients had postinfectious (22.4%) or myelomeningocele-associated (16%) hydrocephalus. Patients' mean head circumference on admission was 51.4 ± 6.3 cm. Their median age at shunt surgery was 137 days, and 22.4% of the patients were operated on without having undergone radiological assessment. The majority of shunts were placed in a right parietooccipital location. Thirteen patients had undergone a previous intraventricular endoscopic procedure. Overall, at least one surgical complication was found in 33.6% of patients up to the first follow-up assessment (median follow-up time of 70 days); shunt infection was the most common complication. The postoperative mortality rate was 9%. The risk factors associated with early surgical complications were tumor-related etiology, larger head circumference, and postoperative hospital stays of greater duration. CONCLUSIONS In a region of the continent where most infant hydrocephalus cases had an uncertain etiology, most patients presented to the hospital in a late stage, with no prenatal diagnosis and with large head circumferences. Standard preoperative investigations were not uniformly performed, and the surgical complications, led by VPS infection, were disturbingly high. Younger patient age, previous endoscopic procedure, surgeon involved, and cranial location of the VPS had no statistical relation to the surgical complications. This study shows that the positive results previously reported by SSA mission hospitals, subspecialized in pediatric neurosurgery, are still not generalizable to every hospital in East Africa. To improve maternal and neonatal care in the Lake region of Tanzania, the development of a fluxogram to determine hydrocephalus etiology, a strict perioperative protocol for VPS insertion, and an increase in the number of endoscopic procedures are recommended to BMC.

Delayed hypertrophic differentiation of epiphyseal chondrocytes contributes to failed secondary ossification in mucopolysaccharidosis VII dogs.

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient ß-glucuronidase activity, which leads to the accumulation of incompletely degraded glycosaminoglycans (GAGs). MPS VII patients present with severe skeletal abnormalities, which are particularly prevalent in the spine. Incomplete cartilage-to-bone conversion in MPS VII vertebrae during postnatal development is associated with progressive spinal deformity and spinal cord compression. The objectives of this study were to determine the earliest postnatal developmental stage at which vertebral bone disease manifests in MPS VII and to identify the underlying cellular basis of impaired cartilage-to-bone conversion, using the naturally-occurring canine model. Control and MPS VII dogs were euthanized at 9 and 14 days-of-age, and vertebral secondary ossification centers analyzed using micro-computed tomography, histology, qPCR, and protein immunoblotting. Imaging studies and mRNA analysis of bone formation markers established that secondary ossification commences between 9 and 14 days in control animals, but not in MPS VII animals. mRNA analysis of differentiation markers revealed that MPS VII epiphyseal chondrocytes are unable to successfully transition from proliferation to hypertrophy during this critical developmental window. Immunoblotting demonstrated abnormal persistence of Sox9 protein in MPS VII cells between 9 and 14 days-of-age, and biochemical assays revealed abnormally high intra and extracellular GAG content in MPS VII epiphyseal cartilage at as early as 9 days-of-age. In contrast, assessment of vertebral growth plates and primary ossification centers revealed no significant abnormalities at either age. The results of this study establish that failed vertebral bone formation in MPS VII can be traced to the failure of epiphyseal chondrocytes to undergo hypertrophic differentiation at the appropriate developmental stage, and suggest that aberrant processing of Sox9 protein may contribute to this cellular dysfunction. These results also highlight the importance of early diagnosis and therapeutic intervention to prevent the progression of debilitating skeletal disease in MPS patients.

A survey of the natural variation in biomechanical and cell wall properties in inflorescence stems reveals new insights into the utility of Arabidopsis as a wood model.

The natural trait variation in Arabidopsis thaliana (L.) Heynh. accessions is an important resource for understanding many biological processes but it is underexploited for wood-related properties. Twelve A. thaliana accessions from diverse geographical locations were examined for variation in secondary growth, biomechanical properties, cell wall glycan content, cellulose microfibril angle (MFA) and flowering time. The effect of daylength was also examined. Secondary growth in rosette and inflorescence stems was observed in all accessions. Organised cellulose microfibrils in inflorescence stems were found in plants grown under long and short days. A substantial range of phenotypic variation was found in biochemical and wood-related biophysical characteristics, particularly for tensile strength, tensile stiffness, MFA and some cell wall components. The four monosaccharides galactose, arabinose, rhamnose and fucose strongly correlated with each other as well as with tensile strength and MFA, consistent with mutations in arabinogalactan protein and fucosyl- and xyloglucan galactosyl-transferase genes that result in decreases in strength. Conversely, these variables showed negative correlations with lignin content. Our data support the notion that large-scale natural variation studies of wood-related biomechanical and biochemical properties of inflorescence stems will be useful for the identification of novel genes important for wood formation and quality, and therefore biomaterial and renewable biofuel production.

Developmental incompetence to stand trial in juvenile courts.

Juveniles' competency to participate in delinquency proceedings has received increased attention in recent years. Developmental incompetence, whereby juveniles' incompetency is based upon their immaturity, as opposed to a mental disorder or developmental disability, is an evolving and important aspect of this area of law. The following paper reviews theories used to support the notion of developmental incompetence, as well as the extant empirical research on juveniles' competency-related abilities. Using a LexisNexis search, statutory and case laws pertaining to juvenile competency were identified across the 50 states and the District of Columbia. Only six states clearly allow developmental incompetence, whereas 17 have laws that do not include developmental immaturity as an acceptable basis of incompetence in juvenile courts. Developmental incompetence is likely to affect a relatively small proportion of juvenile cases, but has important implications for juvenile forensic practice. Recommendations are offered for forensic practitioners conducting this type of evaluation.

Effect of carbamazepine initiation and discontinuation on antithrombotic control in a patient receiving warfarin: case report and review of the literature.

A 72-year-old Caucasian woman with paroxysmal atrial fibrillation had been taking warfarin therapy for 5 years with a stable international normalized ratio (INR). Her dentist then prescribed carbamazepine 200 mg/day to control facial nerve pain. At her next physician visit about 2 weeks after the start of the carbamazepine, the patient's INR had dropped from 3.3 to 1.3; she reported no contributing changes in her diet or warfarin dosage, nor had she taken other interacting drugs. Her warfarin dosage was increased, and the INR returned to the target range of 2.0-3.0 approximately 2 months later. The patient's INR remained stable for approximately 6 more months, until she had facial surgery. During that time, her warfarin was discontinued for 5 days, and the patient had stopped taking the carbamazepine because she had no pain. One month later, her INR increased from 2.2 to 3.6. She did not experience any thrombotic or hemorrhagic episodes. Warfarin undergoes hepatic metabolism through cytochrome P450 2C9, and carbamazepine induces this isoenzyme. Inducing warfarin metabolism necessitates an increase in the warfarin dosage to maintain the INR in the therapeutic target range. To our knowledge, this is the first report documenting the effect of the carbamazepine initiation and discontinuation in a patient receiving anticoagulation therapy with warfarin. In patients taking warfarin, clinicians should monitor the INR closely when carbamazepine is started or discontinued, or when either dosage is changed.

Gain-of-function phenotypes of many CLAVATA3/ESR genes, including four new family members, correlate with tandem variations in the conserved CLAVATA3/ESR domain.

Secreted peptide ligands are known to play key roles in the regulation of plant growth, development, and environmental responses. However, phenotypes for surprisingly few such genes have been identified via loss-of-function mutant screens. To begin to understand the processes regulated by the CLAVATA3 (CLV3)/ESR (CLE) ligand gene family, we took a systems approach to gene identification and gain-of-function phenotype screens in transgenic plants. We identified four new CLE family members in the Arabidopsis (Arabidopsis thaliana) genome sequence and determined their relative transcript levels in various organs. Overexpression of CLV3 and the 17 CLE genes we tested resulted in premature mortality and/or developmental timing delays in transgenic Arabidopsis plants. Overexpression of 10 CLE genes and the CLV3 positive control resulted in arrest of growth from the shoot apical meristem (SAM). Overexpression of nearly all the CLE genes and CLV3 resulted in either inhibition or stimulation of root growth. CLE4 expression reversed the SAM proliferation phenotype of a clv3 mutant to one of SAM arrest. Dwarf plants resulted from overexpression of five CLE genes. Overexpression of new family members CLE42 and CLE44 resulted in distinctive shrub-like dwarf plants lacking apical dominance. Our results indicate the capacity for functional redundancy of many of the CLE ligands. Additionally, overexpression phenotypes of various CLE family members suggest roles in organ size regulation, apical dominance, and root growth. Similarities among overexpression phenotypes of many CLE genes correlate with similarities in their CLE domain sequences, suggesting that the CLE domain is responsible for interaction with cognate receptors.

Ethylene-binding activity, gene expression levels, and receptor system output for ethylene receptor family members from Arabidopsis and tomato.

Ethylene signaling in plants is mediated by a family of ethylene receptors related to bacterial two-component regulators. Expression in yeast of ethylene-binding domains from the five receptor isoforms from Arabidopsis thaliana and five-receptor isoforms from tomato confirmed that all members of the family are capable of high-affinity ethylene-binding activity. All receptor isoforms displayed a similar level of ethylene binding on a per unit protein basis, while members of both subfamily I and subfamily II from Arabidopsis showed similar slow-release kinetics for ethylene. Quantification of receptor-isoform mRNA levels in receptor-deficient Arabidopsis lines indicated a direct correlation between total message level and total ethylene-binding activity in planta. Increased expression of remaining receptor isoforms in receptor-deficient lines tended to compensate for missing receptors at the level of mRNA expression and ethylene-binding activity, but not at the level of receptor signaling, consistent with specialized roles for family members in receptor signal output.

Multiple hormones act sequentially to mediate a susceptible tomato pathogen defense response.

Phytohormones regulate plant responses to a wide range of biotic and abiotic stresses. How a limited number of hormones differentially mediate individual stress responses is not understood. We have used one such response, the compatible interaction of tomato (Lycopersicon esculentum) and Xanthomonas campestris pv vesicatoria (Xcv), to examine the interactions of jasmonic acid (JA), ethylene, and salicylic acid (SA). The role of JA was assessed using an antisense allene oxide cyclase transgenic line and the def1 mutant to suppress Xcv-induced biosynthesis of jasmonates. Xcv growth was limited in these lines as was subsequent disease symptom development. No increase in JA was detected before the onset of terminal necrosis. The lack of a detectable increase in JA may indicate that an oxylipin other than JA regulates basal resistance and symptom proliferation. Alternatively, there may be an increase in sensitivity to JA or related compounds following infection. Hormone measurements showed that the oxylipin signal must precede subsequent increases in ethylene and SA accumulation. Tomato thus actively regulates the Xcv-induced disease response via the sequential action of at least three hormones, promoting expansive cell death of its own tissue. This sequential action of jasmonate, ethylene, and SA in disease symptom development is different from the hormone interactions observed in many other plant-pathogen interactions.

Susceptible to intolerance--a range of hormonal actions in a susceptible Arabidopsis pathogen response.

Ethylene and salicylic acid (SA) are key intermediates in a host's response to pathogens. Previously, we have shown using a tomato compatible interaction that ethylene and SA act sequentially and are essential for disease symptom production. Here, we have examined the relationship between the two signals in the Arabidopsis-Xanthomonas campestris pv. campestris (Xcc) compatible interaction. Preventing SA accumulation by expression of the nahG gene reduced subsequent ethylene production and altered the development of disease symptoms, with plants showing no visible chlorosis. The ethylene insensitive lines, etr1-1 and etr2-1, on the other hand, accumulated SA and exhibited normal but precocious symptom development. Therefore, Arabidopsis, like tomato, was found to exhibit co-operative ethylene and SA action for the production of disease symptoms. However, in Arabidopsis, SA was found to act upstream of ethylene. Jasmonic acid and indole-3-acetic acid levels were also found to increase in response to Xcc. In contrast to ethylene, accumulation of these hormones was not found to be dependent on SA action. These results indicate that the plants response to a virulent pathogen is a composite of multiple signaling pathways.