Atypical audiovisual speech integration in infants at risk for autism

The language difficulties often seen in individuals with autism might stem from an inability to integrate audiovisual information, a skill important for language development. We investigated whether 9-month-old siblings of older children with autism, who are at an increased risk of developing autism, are able to integrate audiovisual speech cues. We used an eye-tracker to record where infants looked when shown a screen displaying two faces of the same model, where one face is articulating/ba/and the other/ga/, with one face congruent with the syllable sound being presented simultaneously, the other face incongruent. This method was successful in showing that infants at low risk can integrate audiovisual speech: they looked for the same amount of time at the mouths in both the fusible visual/ga/− audio/ba/and the congruent visual/ba/− audio/ba/displays, indicating that the auditory and visual streams fuse into a McGurk-type of syllabic percept in the incongruent condition. It also showed that low-risk infants could perceive a mismatch between auditory and visual cues: they looked longer at the mouth in the mismatched, non-fusible visual/ba/− audio/ga/display compared with the congruent visual/ga/− audio/ga/display, demonstrating that they perceive an uncommon, and therefore interesting, speech-like percept when looking at the incongruent mouth (repeated ANOVA: displays x fusion/mismatch conditions interaction: F(1,16) = 17.153, p = 0.001). The looking behaviour of high-risk infants did not differ according to the type of display, suggesting difficulties in matching auditory and visual information (repeated ANOVA, displays x conditions interaction: F(1,25) = 0.09, p = 0.767), in contrast to low-risk infants (repeated ANOVA: displays x conditions x low/high-risk groups interaction: F(1,41) = 4.466, p = 0.041). In some cases this reduced ability might lead to the poor communication skills characteristic of autism

Preliminary effects and acceptability of a co-produced physical activity referral intervention

Objectives: To explore the preliminary effects and acceptability of a co-produced physical activity referral intervention. Study Design: Longitudinal design with data collected at baseline and post a 12-week physical activity referral intervention. Setting. Community leisure centre. Methods: 32 adults with controlled lifestyle-related health conditions took part in a physical activity referral intervention (co-produced by a multidisciplinary stakeholder group) comprising 12 weeks’ subsidised fitness centre access plus four behaviour change consultations. A complete case analysis (t-tests and magnitude-based inferences) was conducted to assess baseline-to-12-week change in physical activity, cardiometabolic, and psychological measures. Semi-structured interviews were conducted (n=12) to explore experiences of the intervention. Results: Mean improvements were observed in cardiorespiratory fitness-2 (3.6 ml.kg.-1min-1 (95% confidence interval 1.9 to 5.4) P<0.001) and moderate-to-vigorous physical activity (12.6 min.day (95% CI 4.3 to 29.6) P=0.013). Participants were positive about the support from exercise referral practitioners, but experienced some challenges in a busy and under staffed gym environment. Conclusions: A co-produced physical activity referral intervention elicited short-term improvements in physical activity and cardiometabolic health. Further refinements may be required, via ongoing feedback between stakeholders, researchers and service users, to achieve the intended holistic physical activity focus of the intervention, prior to a definitive trial

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Intermittent auscultation versus continuous fetal monitoring: Exploring factors that influence birthing unit nurses' fetal surveillance practice using theoretical domains framework

Background: Intermittent Auscultation (IA) is the recommended method of fetal surveillance for healthy women in labour. However, the majority of women receive continuous electronic monitoring. We used the Theoretical Domains Framework (TDF) to explore the views of Birthing Unit nurses about using IA as their primary method of fetal surveillance for healthy women in labour. Methods: Using a semi-structured interview guide, we interviewed a convenience sample of birthing unit nurses throughout Ontario, Canada to elicit their views about fetal surveillance. Interviews were recorded and transcribed verbatim. Transcripts were content analysed using the TDF and themes were framed as belief statements. Domains potentially key to changing fetal surveillance behaviour and informing intervention design were identified by noting the frequencies of beliefs, content, and their reported influence on the use of IA Results: We interviewed 12 birthing unit nurses. Seven of the 12 TDF domains were perceived to be key to changing birthing unit nurses' behaviour The nurses reported that competing tasks, time constraints and the necessity to multitask often limit their ability to perform IA (domains Beliefs about capabilities; Environmental context and resources). Some nurses noted the decision to use IA was something that they consciously thought about with every patient while others stated it their default decision as long as there were no risk factors (Memory, attention and decision processes, Nature of behaviour). They identified positive consequences (e.g. avoid unnecessary interventions, mother-centered care) and negative consequences of using IA (e.g. legal concerns) and reported that the negative consequences can often outweigh positive consequences (Beliefs about consequences). Some reported that hospital policies and varying support from care teams inhibited their use of IA (Social influences), and that support from the entire team and hospital management would likely increase their use (Social influences; Behavioural regulation). Conclusion: We identified potential influences on birthing unit nurses' use of IA as their primary method of fetal surveillance. These beliefs suggest potential targets for behaviour change interventions to promote IA use

Nuclear Mitochondrial DNA Activates Replication in Saccharomyces cerevisiae

The nuclear genome of eukaryotes is colonized by DNA fragments of mitochondrial origin, called NUMTs. These insertions have been associated with a variety of germ-line diseases in humans. The significance of this uptake of potentially dangerous sequences into the nuclear genome is unclear. Here we provide functional evidence that sequences of mitochondrial origin promote nuclear DNA replication in Saccharomyces cerevisiae. We show that NUMTs are rich in key autonomously replicating sequence (ARS) consensus motifs, whose mutation results in the reduction or loss of DNA replication activity. Furthermore, 2D-gel analysis of the mrc1 mutant exposed to hydroxyurea shows that several NUMTs function as late chromosomal origins. We also show that NUMTs located close to or within ARS provide key sequence elements for replication. Thus NUMTs can act as independent origins, when inserted in an appropriate genomic context or affect the efficiency of pre-existing origins. These findings show that migratory mitochondrial DNAs can impact on the replication of the nuclear region they are inserted in

A systematic review of the reporting of Data Monitoring Committees' roles, interim analysis and early termination in pediatric clinical trials

<p>Abstract</p> <p>Background</p> <p>Decisions about interim analysis and early stopping of clinical trials, as based on recommendations of Data Monitoring Committees (DMCs), have far reaching consequences for the scientific validity and clinical impact of a trial. Our aim was to evaluate the frequency and quality of the reporting on DMC composition and roles, interim analysis and early termination in pediatric trials.</p> <p>Methods</p> <p>We conducted a systematic review of randomized controlled clinical trials published from 2005 to 2007 in a sample of four general and four pediatric journals. We used full-text databases to identify trials which reported on DMCs, interim analysis or early termination, and included children or adolescents. Information was extracted on general trial characteristics, risk of bias, and a set of parameters regarding DMC composition and roles, interim analysis and early termination.</p> <p>Results</p> <p>110 of the 648 pediatric trials in this sample (17%) reported on DMC or interim analysis or early stopping, and were included; 68 from general and 42 from pediatric journals. The presence of DMCs was reported in 89 of the 110 included trials (81%); 62 papers, including 46 of the 89 that reported on DMCs (52%), also presented information about interim analysis. No paper adequately reported all DMC parameters, and nine (15%) reported all interim analysis details. Of 32 trials which terminated early, 22 (69%) did not report predefined stopping guidelines and 15 (47%) did not provide information on statistical monitoring methods.</p> <p>Conclusions</p> <p>Reporting on DMC composition and roles, on interim analysis results and on early termination of pediatric trials is incomplete and heterogeneous. We propose a minimal set of reporting parameters that will allow the reader to assess the validity of trial results.</p

Towards Probabilistic Reasoning in Type Theory - The Intersection Type Case

The development of different probabilistic models of uncertainty has been inspired by the rapid progress in various fields, e.g. in AI, probabilistic programming, etc. Lambda calculus is a universal model of computation suitable to express programming languages concepts. Hence, different methods for probabilistic reasoning in lambda calculus have been investigated. In this paper, we develop a formal model for probabilistic reasoning about lambda terms with intersection types, which is a combination of lambda calculus and probabilistic logic. The language of lambda calculus with intersection types is endowed with a probabilistic operator. We propose a semantics based on the possible world approach. An infinitary axiomatization is given for this system and it is proved to be sound with respect to the proposed semantics