Internet cognitive behavioural therapy for panic disorder : does the inclusion of stress management information improve end-state functioning?

Previous research has established Internet-based cognitive behavioural therapy (CBT) for panic disorder (PD) as effective in reducing panic severity and frequency. There is evidence, however, that such programs are less effective at improving overall end-state functioning, defined by a PD clinician severity rating of ≤2 and panic free. In order to test the effect on end-state functioning of the incorporation of stress management material within a CBT program for PD, 32 people with PD were randomised to either Internet-based CBT (PO1), Internet-based CBT plus stress management (PO2) or an Internet-based information-only control condition (IC). Both CBT treatments were more effective at posttreatment assessment than the control condition in reducing PD severity, panic and agoraphobia-related cognition, negative affect and self-ratings of health. PO2 was more effective than PO1 at posttreatment assessment on PD severity and general anxiety, although at 3-month follow-up these differences were no longer apparent. This study provides further support for the efficacy of Internet-based CBT for PD and suggests that although the incorporation of stress management material confers short-term advantages over a standard program, it is not associated with any longer term improvements on panic severity and related cognitions, negative affect, general wellbeing and end-state functioning.

The P-Loop domain of yeast Clp1 mediates interactions between CF IA and CPF factors in Pre-mRNA 3′ end formation

 Cleavage factor IA (CF IA), cleavage and polyadenylation factor (CPF), constitute major protein complexes required for pre-mRNA 3' end formation in yeast. The Clp1 protein associates with Pcf11, Rna15 and Rna14 in CF IA but its functional role remained unclear. Clp1 carries an evolutionarily conserved P-loop motif that was previously shown to bind ATP. Interestingly, human and archaean Clp1 homologues, but not the yeast protein, carry 5' RNA kinase activity. We show that depletion of Clp1 in yeast promoted defective 3' end formation and RNA polymerase II termination; however, cells expressing Clp1 with mutant P-loops displayed only minor defects in gene expression. Similarly, purified and reconstituted mutant CF IA factors that interfered with ATP binding complemented CF IA depleted extracts in coupled in vitro transcription/3' end processing reactions. We found that Clp1 was required to assemble recombinant CF IA and that certain P-loop mutants failed to interact with the CF IA subunit Pcf11. In contrast, mutations in Clp1 enhanced binding to the 3' endonuclease Ysh1 that is a component of CPF. Our results support a structural role for the Clp1 P-loop motif. ATP binding by Clp1 likely contributes to CF IA formation and cross-factor interactions during the dynamic process of 3' end formation.

Coupled RNA polymerase II transcription and 3′ end formation with yeast whole-cell extracts

 RNA polymerase II (RNAP II) transcription and pre-mRNA 3' end formation are linked through physical and functional interactions. We describe here a highly efficient yeast in vitro system that reproduces both transcription and 3' end formation in a single reaction. The system is based on simple whole-cell extracts that were supplemented with a hybrid Gal4-VP16 transcriptional activator and supercoiled plasmid DNA templates encoding G-less cassette reporters. We found that the coupling of transcription and processing in vitro enhanced pre-mRNA 3' end formation and reproduced requirements for poly(A) signals and polyadenylation factors. Unexpectedly, however, we show that in vitro transcripts lacked m⁷G-caps. Reconstitution experiments with CF IA factor assembled entirely from heterologous components suggested that the CTD interaction domain of the Pcf11 subunit was required for proper RNAP II termination but not 3' end formation. Moreover, we observed reduced termination activity associated with extracts prepared from cells carrying a mutation in the 5'-3' exonuclease Rat1 or following chemical inhibition of exonuclease activity. Thus, in vitro transcription coupled to pre-mRNA processing recapitulates hallmarks of poly(A)-dependent RNAP II termination. The in vitro transcription/processing system presented here should provide a useful tool to further define the role of factors involved in coupling.

Diabetes and end-of-life care: ethical issues, practices and challenges

Abstract:
Diabetes is the most significant chronic disease and the global prevalence is increasing. Diabetes is associated with debilitating long term complications and other comorbidities that cause high rates of morbidity and mortality. Keeping blood glucose and other metabolic parameters within an acceptable, personalised range is important to comfort and quality of life but can be challenging, especially during end-of-life care. Guidelines can help clinicians make appropriate care decisions; however, there is little research about what constitutes best practice diabetes care at the end-of-life: existing recommendations and guidelines blend the best available evidence with consensus opinion. In addition, there are important ethical and methodological considerations concerning research involving vulnerable people at the end-of-life. Chapter 3 describes the ethical and methodological issues that needed to be considered when developing guidelines for managing diabetes at the end-of-life and the contribution interviews with dying people and their family carers made to developing a guiding philosophy and to person-centred guidelines.

Reluctant relaxation: The end of the iron ore export embargo and the origins of Australia's mining boom, 1960-1966

The Australian government embargoed any export of iron ore between 1938 and 1960. Joseph Lyons’s government imposed the ban on the eve of World War II for a strategic reason: to prevent the Japanese from importing ore from Yampi Sound in Western Australia. Another consideration, which underpinned the retention of the ban for more than two decades, was the Commonwealth of Australia's perception that Australia's iron ore reserves were limited. In the space of a few years after the partial lifting of the embargo in 1960, world-class reserves of iron ore, mainly in Western Australia, were discovered. Mined and exported from the mid-1960s, iron ore would become, in time, Australia’s best export earner. This article explores the reasons behind the lifting of the ban and how the relaxation of the embargo in stages between 1960 and 1966 shaped the emerging iron ore industry and therefore Australia’s mining boom.