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Discovery as well as optimisation of covalent EGFR T790M/L858R mutant inhibitors.
Young children and adolescents who screened positive for anxiety, depression, and severe impairment had 3-6 and 2-4 times the odds of more office visits respectively. Emergency department utilization was significantly increased in adolescents with anxiety and younger children with severe impairment. CONCLUSIONS This study shows that children with emotional and behavioral disorders are more likely to have increased office visits and missed days of school, even after adjusting for sociodemographic factors and co-morbid medical conditions. Recognition of early associations of emotional and behavioral disorders can create an opportunity for early identification of children with emotional and behavioral disorders in the pediatric practice. OBJECTIVE To determine if use of a health literacy low-inference, self-assessment measure (LISAM), promoted behavior change as measured by increased use of health literacy communication skills (HLCS). METHODS The LISAM is a tool used by educators to self-assess their performances after giving a lecture. The tool is low inference because it self-assesses behaviors that are specific, with little room for subjectivity. Forty-four third-year medical students self-assessed HLCS using a LISAM modified to include health literacy communication skills (LISAM-HLCS). Self-assessment followed participation in an audiotaped, standardized patient encounter and again after listening to the recording. Students also created three written goals for improvement. This session was repeated one week later. RESULTS At Session two, 71.4% of students met at least two of their three self-created objectives. The three most commonly created objectives were using teach-back, asking more open ended questions, and obtaining patient input into the management plan. Use of the LISAM increased HLCS use at Session two vs. Session one as assessed by both students and study investigators (p less then 0.05). CONCLUSIONS Without faculty present, students met and adjusted objectives, catalyzing changes in HLCS. The LISAM-HLCS has the potential to empower students to improve communication skills and to reduce dependence on faculty observations. OBJECTIVE To characterize how pediatric resident self-evaluation compares to standardized patient evaluations in simulated child death disclosure scenarios. STUDY DESIGN This was a prospective, observational, mixed-methods study in which 18 PGY-2 pediatric residents delivered the news of a death of a child to a trained standardized patient (SP) couple. The SPs evaluated residents via a quantitative global rating (1 to 3 scale) and via qualitative comments. Following the training, the residents completed self-assessments consisting of a global rating, qualitative comments, and their confidence related to five death disclosure skills. RESULTS Agreement between SPs and resident ratings was poor; resident scores were compared to each of their two SP evaluators yielding Kappa coefficients of -0.23 (95% CI = -0.60 to -0.07) and -0.30 (95% CI = -0.70 to -0.04). Residents uniformly rated themselves as less capable in their communication skills than SPs did. Residents reported significant increases in their confidence in discussing autopsy and organ donation. Major themes determined from the qualitative comments from SPs included non-verbal communication, verbal communication, attunement to parents, and management of next steps. Residents' comments mirrored these themes with the exception of the absence of non-verbal communication. CONCLUSIONS Pediatric residents underestimated their abilities in a self-assessment of their performance in a SP death disclosure scenario, demonstrating the importance of external feedback, particularly from SPs themselves. Based on SP feedback, future death disclosure trainings should emphasize non-verbal communication skills and specific behaviors that convey effective attunement to families. OBJECTIVE Training residents to be scholars is endorsed by leading medical education organizations. Our previous research suggests the scholarly activity (SA) training experience is highly variable across pediatric residency programs, and residents and program directors (PDs) are generally dissatisfied. mTOR inhibitor Understanding how PD and resident views align can help programs better guide resource allocation and improvement efforts. METHODS We conducted cross-sectional surveys of second and third year pediatric residents and PDs at 22 diverse US categorical programs. We compared resident and PD responses to SA training beliefs, barriers, and satisfaction by 2-proportion z tests. We used descriptive statistics to describe resident responses in relation to same-institution PD responses. RESULTS 464 of 771 residents (60.2%) and 22 PDs (100%) responded. Across programs, PDs more strongly agreed that all residents should participate in SA (59% of PDs (n = 13) versus 27% of residents (n = 127), p=0.002). Residents more strongly believed all residents should have protected SA time (91% of residents (n=424) versus 68% of PDs (n=15), p=0.001). PDs more strongly perceived gaps in other resources as barriers, including lack of funding to conduct or present SA (p less then 0.001, p = 0.02), lack of statistical support (p=0.03), and lack of faculty mentorship (p less then 0.001). Within program concordance was low. CONCLUSIONS Discordance exists between PDs and residents with respect to SA participation and necessary resources, particularly, protected time. Programs must help residents identify when SA can be accomplished. Clearer national guidelines around SA training may also be necessary to reduce discordance and improve perceptions. The asp viper Vipera aspis aspis is a venomous snake found in France, and despite its medical importance, the complete toxin repertoire produced is unknown. Here, we used a venomics approach to decipher the composition of its venom. Transcriptomic analysis revealed 80 venom-annotated sequences grouped into 16 gene families. Among the most represented toxins were snake venom metalloproteases (23%), phospholipases A2 (15%), serine proteases (13%), snake venom metalloprotease inhibitors (13%) and C-type lectins (12%). LC-MS of venoms revealed similar profiles regardless of the method of extraction (milking vs defensive bite). Proteomic analysis validated 57 venom-annotated transcriptomic sequences (>70%), including one for each of the 16 families, but also identified 7 sequences not initially annotated as venom proteins, including a serine protease, a disintegrin, a glutaminyl-peptide cyclotransferase, a proactivator polypeptide-like and 3 aminopeptidases. Interestingly, phospholipases A2 were the dominant proten informing the toxinological basis of clinical signs of envenoming. The combination of chemical cross-linking and mass spectrometry is currently a progressive technology for deriving structural information of proteins and protein complexes. In addition, chemical cross-linking is a powerful tool for stabilizing macromolecular complexes for single particle cryo-electron microscopy. Broad pallets of cross-linking chemistry, currently available for the majority of cross-linking experiments, still rely on the amine-reactive N-hydroxysuccinimide esters targeting mainly N-termini and lysine side chains. These cross-linkers are divided into two groups water soluble and water insoluble; and research teams prefer one or another speculating on the benefits of their choice. However, the effect of cross-linker polarity on the outcome of cross-linking reaction has never been studied. Herein, we use both polar (bis(sulfosuccinimidyl) glutarate) and non-polar (disuccinimidyl glutarate) cross-linkers and systematically investigated the impact of cross-linker hydrophobicity on resulting distance constraints, using bovine serum albumin as a model protein. SIGNIFICANCE Even though the amine reactive BS2G and DSG cross-linkers have the same length of spacer and are based on N-hydroxysuccinimidic group, our data showed that each of them formed preferentially different cross-links. We demonstrated that the choice of cross-linker can have a significant impact on the output data for structural characterization of biomolecules. Using equimolar mixtures of DSG with d6-BS2G, and BS2G with d6-DSG, we established that the polar BS2G preferentially bound to polar regions of modified molecule, whereas non-polar DSG bound to hydrophobic regions. This phenomenon established that the mixture of polar and non-polar cross-linkers acted as an efficient tool for the determination of distance constraints in proteins. Odorants can reach olfactory receptor neurons (ORNs) by two routes orthonasally, when volatiles enter the nasal cavity during inhalation/sniffing, and retronasally, when food volatiles released in the mouth pass into the nasal cavity during exhalation/eating. Previous work in humans has shown that both delivery routes of the same odorant can evoke distinct perceptions and patterns of neural responses in the brain. Each delivery route is known to influence specific responses across the dorsal region of the glomerular sheet in the olfactory bulb (OB), but spatial distributions across the entire glomerular sheet throughout the whole OB remain largely unexplored. We used functional MRI (fMRI) to measure and compare activations across the entire glomerular sheet in rat OB resulting from both orthonasal and retronasal stimulations of the same odors. We observed reproducible fMRI activation maps of the whole OB during both orthonasal and retronasal stimuli. However, retronasal stimuli required double the orthonasal odor concentration for similar response amplitudes. Regardless, both the magnitude and spatial extent of activity were larger during orthonasal versus retronasal stimuli for the same odor. Orthonasal and retronasal response patterns show overlap as well as some route-specific dominance. Orthonasal maps were dominant in dorsal-medial regions, whereas retronasal maps were dominant in caudal and lateral regions. These different whole OB encodings likely underlie differences in odor perception between these biologically important routes for odorants among mammals. These results establish the relationships between orthonasal and retronasal odor representations in the rat OB. Musical score reading and word reading have much in common, from their historical origins to their cognitive foundations and neural correlates. In the ventral occipitotemporal cortex (VOT), the specialization of the so-called Visual Word Form Area for word reading has been linked to its privileged structural connectivity to distant language regions. Here we investigated how anatomical connectivity relates to the segregation of regions specialized for musical notation or words in the VOT. In a cohort of professional musicians and non-musicians, we used probabilistic tractography combined with task-related functional MRI to identify the connections of individually defined word- and music-selective left VOT regions. Despite their close proximity, these regions differed significantly in their structural connectivity, irrespective of musical expertise. The music-selective region was significantly more connected to posterior lateral temporal regions than the word-selective region, which, conversely, was significantly more connected to anterior ventral temporal cortex.
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