A consideration of two models of health and safety training for undergraduate chemists

An initial pilot evaluation is presented of students’ awareness of health and safety training provision, and a comparison of two models of health and safety training after a curriculum redesign. The old model focussed on students generating their own COSHH with highly variable approaches to checking understanding across our curriculum. The new model shifted the focus more on student understanding with a more harmonious approach using research-standard safety documentation and assessment processes. The new system has elements of research-connected teaching and authenticity with students finding the research-standard materials accessible. In terms of preparedness, each model has its benefits and some suggestions for future practice are presented

Incorporation of 3-s-phosphorothiolates into oligonucleotides : changing direction for RNA interference.

The main focus of this work falls into two sections. Firstly the synthesis and hybridisation studies of RNA duplexes containing 3'-S-phosphorothiolate (3'-sp) linkages, which are prepared using traditional automated 3'-5' solid-phase phosphoramidite chemistry. Secondly, investigations into the preparation of the 3'-sp linkage using a currently untried 5'-3', or reverse, synthesis approach. Both approaches have potential use in RNA interference (RNAi). For efficient RNAi activity, there are three key points; the small-interfering RNAs (siRNAs) must maintain an A-type helix; one terminus of the duplex is required to be more thermodynamically stable; and the strand whose 5' -end is less stably paired with the opposite strand is chosen as the guide strand. It has also been shown that RNAi activity does not totally rely on the 2' -hydroxyl functionality and can tolerate 2' -deoxy modifications. In terms of the sugar conformations, the 3' -sp linkage populates the RNA-like north conformation, and hence adopts an A-type helical conformation, to a greater extent than natural RNA, even though it lacks the 2' -hydroxyl group. Incorporating of a 3' -sp modifications into the uridine tract of the RNA duplex, 5'- r(GCGU1oGCG):5'-r(CGCA1QCGC),resulted in the thermal duplex stability rising by 1- 1.2 °C per modification. Therefore, by incorporating the 3' -sp linkage into either the 5' -end of the passenger strand, or the 3' -end of the guide strand, it is anticipated that the 3' -sp linkage can act as a compatible modification in RNAi. Using traditional 3'-5' synthesis, up to five 3'-sp linkages have been incorporated into the thymidine tract of 5'-d(GCGT1QGCG),each with a coupling efficiency of -93 %. By using reverse synthesis, it was hoped that the coupling yields could be enhanced so oligomers consisting entirely of 3'-sp modifications could be prepared; these oligomers could potentially be used as siRNA alternatives. We successfully incorporated a single 3'-sp modification into a DNA oligomer, so a proof of principle has been established. The yield of the thiol-phosphoramidite coupling is obviously poor and would need significantly enhancing for this technique to become a viable alternative to the traditionaI3'-5' synthesis. Optimisation studies are currently ongoing. As a small extra investigation, the possibility of synthesising 3'-thiopurine nucleosides was investigated using an enzymatic approach via transglycosilyation reactions. Initial studies indicate that 3'-thiothymidine and its corresponding 3'-thio-deoxyribose-1aphosphate derivative are substrates for thymidine phosphorylase and purine nucleoside phosphorylase, respectively

The sociology of groups and the economics of incentives: theory and evidence on compensation systems

When working together, people engage in non-contractual and informal interactions that constitute the sociology of the group. We use behavioral models and a unique survey of medical groups to analyze how group sociology influences physician incentive pay and behavior. We conclude that informal interactions among group members influence pay practices and behaviors, but the relationship is complex. No single aspect of group sociology is entirely consistent with all the patterns in the data. Factors emphasized in the economic theory of agency, notably risk aversion, also shape pay policies but these factors cannot account for all the observed empirical relationships

The Sociology of Groups and the Economics of Incentives: Theory and Evidence on Compensation Systems

This paper incorporates the sociological concept of group norms' into an economic analysis of pay systems. We use a behavioral microeconomic model and a unique survey of medical groups to examine the theoretical and empirical relationship between group norms and incentive pay. Our findings suggest that, at least for medical groups, norms are binding constraints in the choice of pay practices. While group norms matter, the patterns in the data suggest that they are not all that matters. Analysis of the preferences and activities of individual physicians indicate that factors highlighted by the economic theory of agency, notably income insurance and multi-task considerations, also shape pay policies. The conclusion we draw from these results is that the sociological concept of group norms augments rather than replaces more conventional economic analyses of pay practices.

The nomenclature, definition and classification of discordant atrioventricular connections

Congenitally corrected transposition is a complex cardiac lesion that is often associated with ventricular septal defect, obstruction of the outflow tract of the morphologically left ventricle, and abnormalities of the morphologically tricuspid valve.1,2Nomenclature for this lesion has been variable and confusing.1In this review, we define, and hopefully clarify this terminology. The lesion is a combination of discordant union of the atrial chambers with the ventricles, and the ventricles with the arterial trunks.1,2In rare circumstances, discordant atrioventricular connections can be associated with concordant ventriculo-arterial connections. This malformation has been called "isolated ventricular inversion". The term is less than precise, and the descriptive approach using the phrase "discordant atrioventricular connections with concordant ventriculo-arterial connections" is preferred, as discussed below

Hypoplastic Left Heart Syndrome Current Considerations and Expectations

In the recent era, no congenital heart defect has undergone a more dramatic change in diagnostic approach, management, and outcomes than hypoplastic left heart syndrome (HLHS). During this time, survival to the age of 5 years (including Fontan) has ranged from 50% to 69%, but current expectations are that 70% of newborns born today with HLHS may reach adulthood. Although the 3-stage treatment approach to HLHS is now well founded, there is significant variation among centers. In this white paper, we present the current state of the art in our understanding and treatment of HLHS during the stages of care: 1) pre-Stage I: fetal and neonatal assessment and management; 2) Stage I: perioperative care, interstage monitoring, and management strategies; 3) Stage II: surgeries; 4) Stage III: Fontan surgery; and 5) long-term follow-up. Issues surrounding the genetics of HLHS, developmental outcomes, and quality of life are addressed in addition to the many other considerations for caring for this group of complex patients

Six-Year Neurodevelopmental Outcomes for Children With Single-Ventricle Physiology

OBJECTIVES: To determine if neurodevelopmental deficits in children with single-ventricle physiology change with age and early developmental scores predict 6-year outcomes. METHODS: In the Single Ventricle Reconstruction Trial, Bayley Scales of Infant Development, Second Edition, were administered at 14 months of age, and parents completed the Behavior Assessment System for Children, Second Edition (BASC-2) annually from the ages of 2 to 6 years. Scores were classified as average, at risk, or impaired. We calculated sensitivities, specificities, and positive and negative predictive values of earlier tests on 6-year outcomes. RESULTS: Of 291 eligible participants, 244 (84%) completed the BASC-2 at 6 years; more Single Ventricle Reconstruction participants than expected on the basis of normative data scored at risk or impaired on the BASC-2 Adaptive Skills Index at that evaluation (28.7% vs 15.9%; P < .001). Children with Adaptive Skills Composite scores <2 SD below the mean at the age of 6 were more likely to have had delayed development at 14 months, particularly on the Psychomotor Development Index (sensitivity of 79%). However, the positive predictive value of the 14-month Mental Development Index and Psychomotor Development Index for 6-year BASC-2 Adaptive Scores was low (44% and 36%, respectively). Adaptive Skills Composite score impairments at the age of 6 were poorly predicted by using earlier BASC-2 assessments, with low sensitivities at the ages of 3 (37%), 4 (48%), and 5 years (55%). CONCLUSIONS: Many children with hypoplastic left heart syndrome who have low adaptive skills at the age of 6 years will not be identified by screening at earlier ages. With our findings, we highlight the importance of serial evaluations for children with critical congenital heart disease throughout development

Development and Validation of a Seizure Prediction Model in Neonates Following Cardiac Surgery

BACKGROUND Electroencephalographic seizures (ES) following neonatal cardiac surgery are often subclinical and have been associated with poor outcomes. An accurate ES prediction model could allow targeted continuous electroencephalographic monitoring (CEEG) for high-risk neonates. METHODS Development and validation of ES prediction models in a multi-center prospective cohort where all postoperative neonates with cardiopulmonary bypass (CPB) underwent CEEG. RESULTS ES occurred in 7.4% of neonates (78 of 1053). Model predictors included gestational age, head circumference, single ventricle defect, DHCA duration, cardiac arrest, nitric oxide, ECMO, and delayed sternal closure. The model performed well in the derivation cohort (c-statistic 0.77, Hosmer-Lemeshow p=0.56), with a net benefit (NB) over monitoring all and none over a threshold probability of 2% in decision curve analysis (DCA). The model had good calibration in the validation cohort (Hosmer-Lemeshow, p=0.60); however, discrimination was poor (c-statistic 0.61) and in DCA there was no NB of the prediction model between the threshold probabilities of 8% and 18%. Using a cut-point that emphasized negative predictive value (NPV) in the derivation cohort, 32% (236 of 737) of neonates would not undergo CEEG, including 3.5% (2 of 58) with ES (NPV 99%, sensitivity 97%). CONCLUSIONS In this large prospective cohort, a prediction model of ES in neonates following CPB had good performance in the derivation cohort with a NB in DCA. However, performance in the validation cohort was weak with poor discrimination, calibration, and no NB in DCA. These findings support CEEG monitoring of all neonates following CPB