Nodavirus RNA replication crown architecture reveals proto-crown precursor and viral protein A conformational switching.

Positive-strand RNA viruses replicate their genomes in virus-induced membrane vesicles, and the resulting RNA replication complexes are a major target for virus control. Nodavirus studies first revealed viral RNA replication proteins forming a 12-fold symmetric "crown" at the vesicle opening to the cytosol, an arrangement recently confirmed to extend to distantly related alphaviruses. Using cryoelectron microscopy (cryo-EM), we show that mature nodavirus crowns comprise two stacked 12-mer rings of multidomain viral RNA replication protein A. Each ring contains an ~19 nm circle of C-proximal polymerase domains, differentiated by strikingly diverged positions of N-proximal RNA capping/membrane binding domains. The lower ring is a "proto-crown" precursor that assembles prior to RNA template recruitment, RNA synthesis, and replication vesicle formation. In this proto-crown, the N-proximal segments interact to form a toroidal central floor, whose 3.1 Å resolution structure reveals many mechanistic details of the RNA capping/membrane binding domains. In the upper ring, cryo-EM fitting indicates that the N-proximal domains extend radially outside the polymerases, forming separated, membrane-binding "legs." The polymerase and N-proximal domains are connected by a long linker accommodating the conformational switch between the two rings and possibly also polymerase movements associated with RNA synthesis and nonsymmetric electron density in the lower center of mature crowns. The results reveal remarkable viral protein multifunctionality, conformational flexibility, and evolutionary plasticity and insights into (+)RNA virus replication and control.

HIV-1 virological synapse formation enhances infection spread by dysregulating Aurora Kinase B.

HIV-1 spreads efficiently through direct cell-to-cell transmission at virological synapses (VSs) formed by interactions between HIV-1 envelope proteins (Env) on the surface of infected cells and CD4 receptors on uninfected target cells. Env-CD4 interactions bring the infected and uninfected cellular membranes into close proximity and induce transport of viral and cellular factors to the VS for efficient virion assembly and HIV-1 transmission. Using novel, cell-specific stable isotope labeling and quantitative mass spectrometric proteomics, we identified extensive changes in the levels and phosphorylation states of proteins in HIV-1 infected producer cells upon mixing with CD4+ target cells under conditions inducing VS formation. These coculture-induced alterations involved multiple cellular pathways including transcription, TCR signaling and, unexpectedly, cell cycle regulation, and were dominated by Env-dependent responses. We confirmed the proteomic results using inhibitors targeting regulatory kinases and phosphatases in selected pathways identified by our proteomic analysis. Strikingly, inhibiting the key mitotic regulator Aurora kinase B (AURKB) in HIV-1 infected cells significantly increased HIV activity in cell-to-cell fusion and transmission but had little effect on cell-free infection. Consistent with this, we found that AURKB regulates the fusogenic activity of HIV-1 Env. In the Jurkat T cell line and primary T cells, HIV-1 Env:CD4 interaction also dramatically induced cell cycle-independent AURKB relocalization to the centromere, and this signaling required the long (150 aa) cytoplasmic C-terminal domain (CTD) of Env. These results imply that cytoplasmic/plasma membrane AURKB restricts HIV-1 envelope fusion, and that this restriction is overcome by Env CTD-induced AURKB relocalization. Taken together, our data reveal a new signaling pathway regulating HIV-1 cell-to-cell transmission and potential new avenues for therapeutic intervention through targeting the Env CTD and AURKB activity.

Subdomain cryo-EM structure of nodaviral replication protein A crown complex provides mechanistic insights into RNA genome replication.

For positive-strand RNA [(+)RNA] viruses, the major target for antiviral therapies is genomic RNA replication, which occurs at poorly understood membrane-bound viral RNA replication complexes. Recent cryoelectron microscopy (cryo-EM) of nodavirus RNA replication complexes revealed that the viral double-stranded RNA replication template is coiled inside a 30- to 90-nm invagination of the outer mitochondrial membrane, whose necked aperture to the cytoplasm is gated by a 12-fold symmetric, 35-nm diameter "crown" complex that contains multifunctional viral RNA replication protein A. Here we report optimizing cryo-EM tomography and image processing to improve crown resolution from 33 to 8.5 Å. This resolves the crown into 12 distinct vertical segments, each with 3 major subdomains: A membrane-connected basal lobe and an apical lobe that together comprise the ∼19-nm-diameter central turret, and a leg emerging from the basal lobe that connects to the membrane at ∼35-nm diameter. Despite widely varying replication vesicle diameters, the resulting two rings of membrane interaction sites constrain the vesicle neck to a highly uniform shape. Labeling protein A with a His-tag that binds 5-nm Ni-nanogold allowed cryo-EM tomography mapping of the C terminus of protein A to the apical lobe, which correlates well with the predicted structure of the C-proximal polymerase domain of protein A. These and other results indicate that the crown contains 12 copies of protein A arranged basally to apically in an N-to-C orientation. Moreover, the apical polymerase localization has significant mechanistic implications for template RNA recruitment and (-) and (+)RNA synthesis.

Aptitude and attitude: predictors of performance during and after basic laparoscopic skills training.

BACKGROUND: Manual dexterity and visual-spatial ability are considered key to the development of superior laparoscopic skills. Nevertheless, these abilities do not reliably explain all the variance found in the technical performance of surgical trainees. Consequently, we must look beyond these abilities to improve our understanding of laparoscopic skills and to better identify/develop surgical potential earlier on. PURPOSE: To assess the individual and collective impact of physical, cognitive, visual, and psychological variables on performance during and after basic simulation-based laparoscopic skills training. METHOD: Thirty-four medical students (laparoscopic novices) completed a proficiency-based laparoscopic skills training program (using either a 2D or 3D viewing mode). This was followed by one testing session, a follow-up testing session with new (yet similar) tasks, and a series of physical, cognitive, visual, and psychological measures. RESULTS: The statistical models that best predicted variance in training performance metrics included four variables: viewing mode (2D vs 3D), psychological flexibility, perceived task demands, and manual dexterity (bimanual). In subsequent testing, a model that included viewing mode and manual dexterity (assembly) best predicted performance on the pre-practiced tasks. However, for a highly novel, spatially complex laparoscopic task, performance was best predicted by a model that comprised viewing mode, visual-spatial ability, and perceived task demands. At follow-up, manual dexterity (assembly) alone was the best predictor of performance on new (yet similar) tasks. CONCLUSION: By focussing exclusively on physical/cognitive abilities, we may overlook other important predictors of surgical performance (e.g. psychological variables). The present findings suggest that laparoscopic performance may be more accurately explained through the combined effects of physical, cognitive, visual, and psychological variables. Further, the results suggest that the predictors may change with both task demands and the development of the trainee. This study highlights the key role of psychological skills in overcoming initial training challenges, with far-reaching implications for practice.

Laparoscopic skills training: the effects of viewing mode (2D vs. 3D) on skill acquisition and transfer.

BACKGROUND: Three-dimensional (3D) visual displays have been suggested to aid laparoscopic skills training by providing the depth cues not present in traditional two-dimensional (2D) displays. However, few studies have robustly investigated the impact of viewing mode (2D vs. 3D) on learning outcomes. PURPOSE: To examine how viewing mode (2D vs. 3D) impacts the acquisition and transferability of basic laparoscopic skills by comparing performance between transfer and control groups on a complete proficiency-based training program. METHOD: A counterbalanced between-subjects design was employed. Each participant was randomly allocated to one of four groups, comprising two transfer groups (trained in one viewing mode and tested in the alternate mode: the 2D → 3D and 3D → 2D groups) and two control groups (trained and tested in one viewing mode: the 2D → 2D and 3D → 3D groups). Participants completed proficiency-based training in six laparoscopic training tasks. Testing included two further repetitions of all tasks under test conditions. Objective performance measures included the total number of repetitions to reach proficiency, and total performance scores (i.e. time + error penalties across all repetitions) in training and testing. RESULTS: The groups trained in 3D demonstrated superior training performance (i.e. less time + errors) and took fewer repetitions to reach proficiency than the groups trained in 2D. The groups tested in 3D also demonstrated superior test performance compared to those tested in 2D. However, training mode did not yield significant test differences between the groups tested in 2D (i.e. 2D → 2D vs. 3D → 2D), or between the groups tested in 3D (i.e. 3D → 3D vs. 2D → 3D). CONCLUSION: Novices demonstrate superior performance in laparoscopic skills training using a 3D viewing mode compared to 2D. However, this does not necessarily translate to superior performance in subsequent testing or enhanced learning overall. Rather, test performance appears to be dictated by the viewing mode used during testing, not that of prior training.

Quantitative systematic review: Sources of inaccuracy in manually measured adult respiratory rate data.

AIMS: To identify the potential sources of inaccuracy in manually measured adult respiratory rate (RR) data and quantify their effects. DESIGN: Quantitative systematic review with meta-analyses where appropriate. DATA SOURCES: Medline, CINAHL, and Cochrane Library (from database inception to 31 July 2019). REVIEW METHODS: Studies presenting data on individual sources of inaccuracy in the manual measurement of adult RR were analysed, assessed for quality, and grouped according to the source of inaccuracy investigated. Quantitative data were extracted and synthesized and meta-analyses performed where appropriate. RESULTS: Included studies (N = 49) identified five sources of inaccuracy. The awareness effect creates an artefactual reduction in actual RR, and observation methods involving shorter counts cause systematic underscoring. Individual RR measurements can differ substantially in either direction between observations due to inter- or intra-observer variability. Value bias, where particular RRs are over-represented (suggesting estimation), is a widespread problem. Recording omission is also widespread, with higher average rates in inpatient versus triage/admission contexts. CONCLUSION: This review demonstrates that manually measured RR data are subject to several potential sources of inaccuracy. IMPACT: RR is an important indicator of clinical deterioration and commonly included in track-and-trigger systems. However, the usefulness of RR data depends on the accuracy of the observations and documentation, which are subject to five potential sources of inaccuracy identified in this review. A single measurement may be affected by several factors. Hence, clinicians should interpret recorded RR data cautiously unless systems are in place to ensure its accuracy. For nurses, this includes counting rather than estimating RRs, employing 60-s counts whenever possible, ensuring patients are unaware that their RR is being measured, and documenting the resulting value. For any given site, interventions to improve measurement should take into account the local organizational and cultural context, available resources, and the specific measurement issues that need to be addressed.

Human papillomavirus oncogenes reprogram the cervical cancer microenvironment independently of and synergistically with estrogen.

High-risk human papillomaviruses (HPVs) infect epithelial cells and are causally associated with cervical cancer, but HPV infection is not sufficient for carcinogenesis. Previously, we reported that estrogen signaling in the stromal tumor microenvironment is associated with cervical cancer maintenance and progression. We have now determined how HPV oncogenes and estrogen treatment affect genome-wide host gene expression in laser-captured regions of the cervical epithelium and stroma of untreated or estrogen-treated nontransgenic and HPV-transgenic mice. HPV oncogene expression in the cervical epithelium elicited significant gene-expression changes in the proximal stromal compartment, and estrogen treatment uniquely affected gene expression in the cervical microenvironment of HPV-transgenic mice compared with nontransgenic mice. Several potential estrogen-induced paracrine-acting factors were identified in the expression profile of the cervical tumor microenvironment. The microenvironment of estrogen-treated HPV-transgenic mice was significantly enriched for chemokine/cytokine activity and inflammatory and immune functions associated with carcinogenesis. This inflammatory signature included several proangiogenic CXCR2 receptor ligands. A subset of the same CXCR2 ligands was likewise increased in cocultures of early-passage cells from human cervical samples, with levels highest in cocultures of cervical fibroblasts and cancer-derived epithelial cells. Our studies demonstrate that high-risk HPV oncogenes profoundly reprogram the tumor microenvironment independently of and synergistically with estrogen. These observations illuminate important means by which HPVs can cause cancer through alterations in the tumor microenvironment.

Molecular transitions from papillomavirus infection to cervical precancer and cancer: Role of stromal estrogen receptor signaling.

To study the multistep process of cervical cancer development, we analyzed 128 frozen cervical samples spanning normalcy, increasingly severe cervical intraepithelial neoplasia (CIN1- CIN3), and cervical cancer (CxCa) from multiple perspectives, revealing a cascade of progressive changes. Compared with normal tissue, expression of many DNA replication/repair and cell proliferation genes was increased in CIN1/CIN2 lesions and further sustained in CIN3, consistent with high-risk human papillomavirus (HPV)-induced tumor suppressor inactivation. The CIN3-to-CxCa transition showed metabolic shifts, including decreased expression of mitochondrial electron transport complex components and ribosomal protein genes. Significantly, despite clinical, epidemiological, and animal model results linking estrogen and estrogen receptor alpha (ERα) to CxCa, ERα expression declined >15-fold from normalcy to cancer, showing the strongest inverse correlation of any gene with the increasing expression of p16, a marker for HPV-linked cancers. This drop in ERα in CIN and tumor cells was confirmed at the protein level. However, ERα expression in stromal cells continued throughout CxCa development. Our further studies localized stromal ERα to FSP1+, CD34+, SMA- precursor fibrocytes adjacent to normal and precancerous CIN epithelium, and FSP1-, CD34-, SMA+ activated fibroblasts in CxCas. Moreover, rank correlations with ERα mRNA identified IL-8, CXCL12, CXCL14, their receptors, and other angiogenesis and immune cell infiltration and inflammatory factors as candidates for ERα-induced stroma-tumor signaling pathways. The results indicate that estrogen signaling in cervical cancer has dramatic differences from ERα+ breast cancers, and imply that estrogen signaling increasingly proceeds indirectly through ERα in tumor-associated stromal fibroblasts.

The effects of awareness and count duration on adult respiratory rate measurements: An experimental study.

AIMS AND OBJECTIVES: To investigate whether awareness of manual respiratory rate monitoring affects respiratory rate in adults, and whether count duration influences respiratory rate estimates. BACKGROUND: Nursing textbooks typically suggest that the patient should ideally be unaware of respiratory rate observations; however, there is little published evidence of the effect of awareness on respiratory rate, and none specific to manual measurement. In addition, recommendations about the length of the respiratory rate count vary from text to text, and the relevant empirical evidence is scant, inconsistent and subject to substantial methodological limitations. DESIGN: Experimental study with awareness of respiration monitoring (aware, unaware; randomised between-subjects) and count duration (60 s, 30 s, 15 s; within-subjects) as the independent variables. Respiratory rate (breaths/minute) was the dependent variable. METHODS: Eighty-two adult volunteers were randomly assigned to aware and unaware conditions. In the baseline block, no live monitoring occurred. In the subsequent experimental block, the researcher informed aware participants that their respiratory rate would be counted, and did so. Respirations were captured throughout via video recording, and counted by blind raters viewing 60-, 30- and 15-s extracts. The data were collected in 2015. RESULTS: There was no baseline difference between the groups. During the experimental block, the respiratory rates of participants in the aware condition were an average of 2.13 breaths/minute lower compared to unaware participants. Reducing the count duration from 1 min to 15 s caused respiratory rate to be underestimated by an average of 2.19 breaths/minute (and 0.95 breaths/minute for 30-s counts). The awareness effect did not depend on count duration. CONCLUSIONS: Awareness of monitoring appears to reduce respiratory rate, and shorter monitoring durations yield systematically lower respiratory rate estimates. RELEVANCE TO CLINICAL PRACTICE: When interpreting and acting upon respiratory rate data, clinicians should consider the potential influence of these factors, including cumulative effects.

Assessment of colorectal polyp recognition skill: development and validation of an objective test.

BACKGROUND: The quality of colonoscopy is known to vary. The extent to which colonoscopists can recognize the presence of subtle colorectal lesions by visually distinguishing them from the surrounding mucosa (i.e., polyp recognition skill) may be one of several attributes that influence polyp detection rates. The aim of the present study was to develop and validate the first objective test of polyp recognition skill. METHODS: Validation study. Twenty-eight experienced colonoscopists and eighty novices took a preliminary 280-item computer-based polyp recognition test. Items were genuine endoscopic images which participants assessed for the presence of "likely polyps." Half included clinically identified polyps. Participants clicked on a suspected lesion or a button marked "no likely polyp", and the main outcome measures were accuracy and response latency. The best items were selected for the final 50-item test. RESULTS: In the preliminary test, experienced colonoscopists correctly identified more polyps than novices (P < .0001) and better discriminated between clinically identified polyps and non-polyp features (as measured by d', P < .0001). For polyp items, the experienced group also responded faster (P < .01). Effect sizes were large for accuracy (Cohen's d = 3.22) and d' (Cohen's d = 3.22). The 50 final test items produced comparable results for accuracy, d', and response latency. For both versions of the test, score scale reliability was high for both polyp and non-polyp items (α = .82 to .97). CONCLUSIONS: The observed experienced-novice differences support the construct validity of the performance measures derived from the tests, indicating that polyp recognition skill can be quantified objectively. The final test may potentially be used to assess trainees, but test sensitivity may be insufficient to make fine-grained distinctions between different skill levels among experienced colonoscopists. More sensitive future tests may provide a valuable supplement to clinical detection rates, allowing objective comparisons between skilled colonoscopists.

A novel training device for tip control in colonoscopy: preliminary validation and efficacy as a training tool.

BACKGROUND: Effective control of the colonoscope tip is one of the most fundamental components of colonoscopy skill. Mastering fine tip control can be problematic for novice trainees, yet no validated training regimes exist for developing this specific skill component in isolation. We aimed to conduct a preliminary validation of a novel training device for colonoscopic tip control, and to assess its efficacy as a training tool. METHODS: In study 1 (validation), 13 experienced colonoscopists and 16 novices used a colonoscope to accurately track 28 targets on each of four concave "training surfaces" as quickly as possible, and we compared their performance. In study 2 (pre-post-training study), another 16 novices were tested before and after a six-session training program. In both studies, the main outcome measurements were completion time (measured automatically by the device) and variability of individual performance (the SD of each individual's completion times across trials). RESULTS: Compared with novices, experienced colonoscopists were faster (P < 0.0001) and their performances less variable (P < 0.0001). With training, novices became faster (P < 0.0001) and more consistent (P = 0.003), and these improvements also generalized to novel training surfaces (P's < 0.01). After training, the novices' tip control performance was indistinguishable from that of the experienced colonoscopists (P's > 0.05). The composite measures of completion time used in both studies all had acceptable to excellent internal consistency reliability (α's ranged from 0.72 to 0.93). CONCLUSIONS: We found that performance measures derived from using the device to assess skill can discriminate between experienced colonoscopists and novices in terms of their ability to control and guide the colonoscope tip precisely, providing preliminary evidence to support the construct validity of the metrics. The device is also an effective training tool for this fundamental component of colonoscopy skill.

Assessing colonoscopic inspection skill using a virtual withdrawal simulation: a preliminary validation of performance metrics.

BACKGROUND: The effectiveness of colonoscopy for diagnosing and preventing colon cancer is largely dependent on the ability of endoscopists to fully inspect the colonic mucosa, which they achieve primarily through skilled manipulation of the colonoscope during withdrawal. Performance assessment during live procedures is problematic. However, a virtual withdrawal simulation can help identify and parameterise actions linked to successful inspection, and offer standardised assessments for trainees. METHODS: Eleven experienced endoscopists and 18 endoscopy novices (medical students) completed a mucosal inspection task during three simulated colonoscopic withdrawals. The two groups were compared on 10 performance metrics to preliminarily assess the validity of these measures to describe inspection quality. Four metrics were related to aspects of polyp detection: percentage of polyp markers found; number of polyp markers found per minute; percentage of the mucosal surface illuminated by the colonoscope (≥0.5 s); and percentage of polyp markers illuminated (≥2.5 s) but not identified. A further six metrics described the movement of the colonoscope: withdrawal time; linear distance travelled by the colonoscope tip; total distance travelled by the colonoscope tip; and distance travelled by the colonoscope tip due to movement of the up/down angulation control, movement of the left/right angulation control, and axial shaft rotation. RESULTS: Statistically significant experienced-novice differences were found for 8 of the 10 performance metrics (p's < .005). Compared with novices, experienced endoscopists inspected more of the mucosa and detected more polyp markers, at a faster rate. Despite completing the withdrawals more quickly than the novices, the experienced endoscopists also moved the colonoscope more in terms of linear distance travelled and overall tip movement, with greater use of both the up/down angulation control and axial shaft rotation. However, the groups did not differ in the number of polyp markers visible on the monitor but not identified, or movement of the left/right angulation control. All metrics that yielded significant group differences had adequate to excellent internal consistency reliability (α = .79 to .90). CONCLUSIONS: These systematic differences confirm the potential of the simulated withdrawal task for evaluating inspection skills and strategies. It may be useful for training, and assessment of trainee competence.

Systematic identification of Ctr9 regulome in ERα-positive breast cancer.

BACKGROUND: We had previously identified Ctr9, the key scaffold subunit of the human RNA polymerase II (RNAPII) associated factor complex (PAFc), as a key factor regulating a massive ERα target gene expression and ERα-positive breast cancer growth. Furthermore, we have shown that knockdown of Ctr9 reduces ERα protein stability and decreases the occupancy of ERα and RNAPII at a few ERα-target loci. However, it remains to be determined whether Ctr9 controls ERα-target gene expression by regulating the global chromatin occupancy of ERα and RNAPII in the presence of estrogen. RESULTS: In this study, we determined the genome-wide ERα and RNAPII occupancy in response to estrogen reatment and/or Ctr9 knockdown by performing chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq). We found that loss of Ctr9 dramatically decreases the global occupancy of ERα and RNAPII, highlighting the significance of Ctr9 in regulating estrogen signaling in ERα-positive breast cancer cells. Combining this resource with previously published genomic data sets, we identified a unique subset of ERα and Ctr9 target genes, and further delineated the independent function of Ctr9 from other subunits in PAFc when regulating transcription. CONCLUSIONS: Our data demonstrated that Ctr9, independent of other PAFc subunits, controls ERα-target gene expression by regulating global chromatin occupancies of ERα and RNAPII.

Do self-reported concussions have cumulative or enduring effects on drivers' anticipation of traffic hazards?

AIM: To investigate the cumulative effect of multiple self-reported concussions and the enduring effect of concussion on drivers' hazard perception ability. It was hypothesized: (1) that individuals reporting multiple previous concussions would be slower to anticipate traffic hazards than individuals reporting either one previous concussion or none; and (2) that individuals reporting a concussion within the past 3 months would be slower to anticipate traffic hazards than individuals reporting either an earlier concussion or no prior concussion. METHOD: Two hundred and eighty-two predominantly young drivers (nconcussed = 68, Mage = 21.57 years, SDage = 6.99 years, 66% female) completed a validated hazard perception test (HPT) and measures of emotional, cognitive, health and driving status. RESULTS: A one-way analysis of variance showed that there was no significant effect of concussion number on HPT response times. Similarly, pairwise comparisons showed no significant differences between the HPT response times of individuals reporting a concussion within the previous 3 months, individuals reporting an earlier concussion and the never concussed group. CONCLUSION: The findings suggest that previous concussions do not adversely affect young drivers' ability to anticipate traffic hazards; however, due to reliance on self-reports of concussion history, further prospective longitudinal research is needed.

Observation chart design features affect the detection of patient deterioration: a systematic experimental evaluation.

AIM: To systematically evaluate the impact of several design features on chart-users' detection of patient deterioration on observation charts with early-warning scoring-systems. BACKGROUND: Research has shown that observation chart design affects the speed and accuracy with which abnormal observations are detected. However, little is known about the contribution of individual design features to these effects. DESIGN: A 2 × 2 × 2 × 2 mixed factorial design, with data-recording format (drawn dots vs. written numbers), scoring-system integration (integrated colour-based system vs. non-integrated tabular system) and scoring-row placement (grouped vs. separate) varied within-participants and scores (present vs. absent) varied between-participants by random assignment. METHODS: 205 novice chart-users, tested between March 2011-March 2014, completed 64 trials where they saw real patient data presented on an observation chart. Each participant saw eight cases (four containing abnormal observations) on each of eight designs (which represented a factorial combination of the within-participants variables). On each trial, they assessed whether any of the observations were physiologically abnormal, or whether all observations were normal. Response times and error rates were recorded for each design. RESULTS: Participants responded faster (scores present and absent) and made fewer errors (scores absent) using drawn-dot (vs. written-number) observations and an integrated colour-based (vs. non-integrated tabular) scoring-system. Participants responded faster using grouped (vs. separate) scoring-rows when scores were absent, but separate scoring-rows when scores were present. CONCLUSION: Our findings suggest that several individual design features can affect novice chart-users' ability to detect patient deterioration. More broadly, the study further demonstrates the need to evaluate chart designs empirically.

Less is more: the design of early-warning scoring systems affects the speed and accuracy of scoring.

AIM: To evaluate the effect of early-warning scoring system design on the speed and accuracy of scoring. BACKGROUND: Despite the widespread implementation of early-warning scoring systems in hospitals, the speed and accuracy with which chart-users determine patients' early-warning scores has received minimal research attention. DESIGN: Within-subjects, with scoring-system design as the independent variable. METHODS: Forty-seven novice chart-users were presented with realistic vital sign observations recorded on charts with three different scoring-system designs. The rows for recording individual vital sign scores were either: (1) grouped together beneath all of the vital sign rows; (2) separated, with each row presented immediately below the corresponding vital sign row; or (3) excluded altogether. Participants' response times and error rates for determining the overall scores were measured for 54 time-points per design. Data were collected in December 2012-January 2013. RESULTS: Contrary to predictions, participants responded fastest and made the fewest errors when using the chart design without individual vital sign scoring-rows. For the other two designs, participants were faster when the rows for scoring individual vital signs were separated (vs. grouped), but accuracy did not differ. For both of these designs, significantly more time-points were affected by scoring errors compared with adding errors. Finally, data for patients with more serious derangements yielded greater response times and error rates on all three charts. CONCLUSION: Early-warning scoring systems may be more effective without individual vital sign scoring-rows. Even when charts are designed by multi-disciplinary teams of human factors specialists and clinicians, empirical evaluations are essential.

A competency framework for colonoscopy training derived from cognitive task analysis techniques and expert review.

BACKGROUND: Colonoscopy is a difficult cognitive-perceptual-motor task. Designing an appropriate instructional program for such a task requires an understanding of the knowledge, skills and attitudes underpinning the competency required to perform the task. Cognitive task analysis techniques provide an empirical means of deriving this information. METHODS: Video recording and a think-aloud protocol were conducted while 20 experienced endoscopists performed colonoscopy procedures. "Cued-recall" interviews were also carried out post-procedure with nine of the endoscopists. Analysis of the resulting transcripts employed the constant comparative coding method within a grounded theory framework. The resulting draft competency framework was modified after review during semi-structured interviews conducted with six expert endoscopists. RESULTS: The proposed colonoscopy competency framework consists of twenty-seven skill, knowledge and attitude components, grouped into six categories (clinical knowledge; colonoscope handling; situation awareness; heuristics and strategies; clinical reasoning; and intra- and inter-personal). CONCLUSIONS: The colonoscopy competency framework provides a principled basis for the design of a training program, and for the design of formative assessment to gauge progress towards attaining the knowledge, skills and attitudes underpinning the achievement of colonoscopy competence.

Athletes' age, sex, and years of education moderate the acute neuropsychological impact of sports-related concussion: a meta-analysis.

The objective of this study is to determine which pre-existing athlete characteristics, if any, are associated with greater deficits in functioning following sports-related concussion, after controlling for factors previously shown to moderate this effect (e.g., time since injury). Ninety-one independent samples of concussion were included in a fixed+systematic effects meta-analysis (n = 3,801 concussed athletes; 5,631 controls). Moderating variables were assessed using analogue-to-ANOVA and meta-regression analyses. Post-injury assessments first conducted 1-10 days following sports-related concussion revealed significant neuropsychological dysfunction, postural instability and post-concussion symptom reporting (d = -0.54, -1.10, and -1.14, respectively). During this interval, females (d = -0.87), adolescent athletes competing in high school competitions (d = -0.60), and those with 10 years of education (d = -1.32) demonstrated larger post-concussion neuropsychological deficits than males (d = -0.42), adults (d = -0.25), athletes competing at other levels of competition (d = -0.43 to -0.41), or those with 16 years of education (d = -0.15), respectively. However, these sub-groups' differential impairment/recovery beyond 10 days could not be reliably quantified from available literature. Pre-existing athlete characteristics, particularly age, sex and education, were demonstrated to be significant modifiers of neuropsychological outcomes within 10 days of a sports-related concussion. Implications for return-to-play decision-making and future research directions are discussed.