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Resting state fMRI (rsfMRI) is frequently used to study brain function, including in clinical populations. Similarity of blood-oxygen-level-dependent (BOLD) fluctuations during rsfMRI between brain regions is thought to reflect intrinsic functional connectivity (FC), potentially due to history of coactivation. To quantify similarity, studies have almost exclusively relied on Pearson correlation, which assumes linearity and can therefore underestimate FC if the hemodynamic response function differs regionally or there is BOLD signal lag between timeseries. Here we show in three cohorts of children, adolescents and adults, with and without autism spectrum disorders (ASDs), that measuring the similarity of BOLD signal fluctuations using non-linear dynamic time warping (DTW) is more robust to global signal regression (GSR), has higher test-retest reliability and is more sensitive to task-related changes in FC. Additionally, when comparing FC between individuals with ASDs and typical controls, more group differences are detected using DTW. DTW estimates are also more related to ASD symptom severity and executive function, while Pearson correlation estimates of FC are more strongly associated with respiration during rsfMRI. Together these findings suggest that non-linear methods such as DTW improve estimation of resting state FC, particularly when studying clinical populations whose hemodynamics or neurovascular coupling may be altered compared to typical controls.

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While approximately half of all qualified hospital pharmacist independent prescribers (PIPs) in Scotland are active prescribers, there are major differences in prescribing activity across geographical areas. This study aimed to explore, through focus groups, interviews and a questionnaire, hospital PIPs' perceptions of factors associated with prescribing activity and to investigate the infrastructure required to better support active prescribing by PIPs. Findings reinforced the perceived positive impact of supportive pharmacy leadership within the organisation, recognition that prescribing is integral to the clinical pharmacist role and a work environment conducive to prescribing.

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BACKGROUND AND AIMS: Prescribing errors cause significant patient morbidity and mortality. Current legislation allows prescribing by different health professions. Inter-professional collaboration and learning may result in safer prescribing practice. This study aimed to develop, pilot and test the feasibility of a simulated inter-professional prescribing masterclass for non-medical prescribing students, medical students and pharmacists. METHODS AND RESULTS: A three-scenario, simulated patient session was designed and implemented by an expert panel. Medical students, non-medical prescribing students and pharmacists worked together to formulate and implement evidence-based prescriptions. The Readiness for Inter-professional Learning Score (RIPLS) and a self-efficacy score were administered to the students and the Trust in Physician Score to the simulated patients. Overall, the RIPLS and self-efficacy scores increased. Pharmacists showed the highest rating in the Trust in Physician score. Post masterclass group discussions suggested that the intervention was viewed as a positive educational experience. CONCLUSION: An inter-professional prescribing masterclass is feasible and acceptable to students. It increases self-efficacy, readiness for inter-professional learning and allows students to learn from, about and with each other. A larger study is warranted and the use of feedback from simulated patients explored further.

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A novel and simple preparation of amine-modified γ-Fe2O3 nanoparticles is described. The presence of amine groups on the surface, instead of hydroxyl groups, will allow conjugation of biologically active molecules to the iron oxide nanoparticles without the need for a size increasing silica shell. Furthermore, the outer amine-layer increases the temperature of the γ-Fe2O3 to α-Fe2O3 structural transition in a similar way to previously reported cationic substitutions. This may suggest the formation of an oxide-nitride outer layer. Re-dispersion of the amine-modified γ-Fe2O3 nanoparticles led to the preparation of stable ferrofluids.

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BACKGROUND: Numerous studies have shown that attention deficit/hyperactivity disorder (ADHD) is associated higher risk of cannabis use disorders (CUD). However, these studies are limited in that most did not: (a) differentiate the role of hyperactivity-impulsivity (HI) and inattention (IN); (b) control for associated psychopathology; and (c) consider more fine-grained CUD-related measures. Our aim was to clarify the unique and interactive contributions of inattention and hyperactivity symptoms to age of cannabis initiation and DSM-IV cannabis dependence, craving, and severity of problems related to cannabis use while statistically controlling for symptoms of comorbid psychopathology in a non-clinical sample of young adults. METHODS: Cannabis variables, current use of cigarettes and alcohol, current and childhood ADHD, and comorbid internalizing and externalizing psychopathology were assessed in 376 male and female undergraduates. RESULTS: Results indicate that current and childhood IN were independently associated with more severe cannabis use, craving, and problem use-related outcomes in young adulthood (p's<.01) and that childhood HI symptoms were associated with earlier initiation of cannabis (p<.01). Further, current IN symptoms moderated the relationships between level of use and more severe outcomes (p's<.01), such that higher IN strengthened positive associations among use and problem cannabis use. Associations with ADHD symptom dimensions and current use of alcohol and cigarettes were also present. CONCLUSIONS: Thus, current and childhood inattention symptoms as well as childhood hyperactive-impulsive symptoms emerged as significant factors in cannabis-related outcomes in young adults, even after statistically controlling for important confounding variables.

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A variety of endoscopic haemostatic techniques have enabled major advances in the management of not only bleeding peptic ulcers and bleeding varices, but also in a variety of bleeding lesions in the small intestine and in the colon. Indeed, the development and widespread implementation of endoscopic haemostasis has been one of the most important developments in clinical gastroenterology in the past two decades. An increasingly ageing cohort of patients with multiple co-morbidity are being treated and therefore improving the outcome of gastrointestinal bleeding continues to pose major challenges.

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Intrinsic factor (IF) has been expressed previously in Baculovirus with a yield (0.1-1 mg/l) that was inadequate for structural and metabolic studies. IF cDNAs were cloned into the shuttle vector pPIC9 of P. pastoris, and the proteins were induced and purified by cobalamin (Cbl) affinity chromatography. Expression of recombinant proteins revealed a major band of 49 kDa for both human and rat IF. Expression of human IF was achieved at 1040 mg/l, but of rat IF at only 1-2 mg/l. Reaction of human IF with a photo-activatable derivative of Cbl was demonstrated by Western blotting, and detection of IF fragments by anti-Cbl monoclonal antibody and by amino-terminal sequencing revealed at least three regions (residues 129-151, 234-254, and +294) linked to Cbl. Both recombinant human and rat [125I]IF-Cbl bound to rat and guinea pig brush border membranes with similar affinity, but the binding capacity of human IF for the rat receptor was only 10% compared with rat IF. All six amino acids within the previously identified N-terminal binding region of human IF were mutated to be identical to rat IF, but the resulting chimeric IF still bound poorly to rat membranes. Mutations of residues 26/27 (Glu26 to Asp and Asn27 to Gln) and 32/34 (Ser32 to Thr and Tyr34 to Arg) showed changes in both Ka and Vmax, with great effects on Vmax. In conclusion, P. pastoris is an expression system that produces functional human IF at a higher yield than in the baculovirus system. Cbl binding was directly demonstrated at multiple sites along the linear sequence of human IF. The receptor binding function of the amino terminal sequence 25 62 has been confirmed, but it is insufficient to reproduce all the features of IF-Cbl binding.

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To obtain a set of microsatellite markers for the Queensland fruit fly Bactrocera tryoni, a genomic library was screened with a number of simple repeat oligonucleotide probes. Sequencing recovered 22 repeat loci. The microsatellite sequences were short, with repeat numbers ranging from five to 11. Of these, 16 polymerase chain reaction (PCR) primer sets yielded amplifiable products, which were tested on 53 flies from five widely separated sites. All loci showed polymorphism in the population sample, with the number of alleles ranging from two to 16. Several dinucleotide repeats showed alleles separated by single-base differences and multiple steps, suggesting a mutation process more complex than the stepwise mutation model.

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