PRehabIlitatiOn with pReoperatIve exercise and educaTion for patients undergoing major abdominal cancer surgerY: protocol for a multicentre randomised controlled TRIAL (PRIORITY TRIAL)

Background Radical surgery is the mainstream treatment for patients presenting with advanced primary or recurrent gastrointestinal cancers; however, the rate of postoperative complications is exceptionally high. The current evidence suggests that improving patients’ fitness during the preoperative period may enhance postoperative recovery. Thus, the primary aim of this study is to establish the effectiveness of prehabilitation with a progressive, individualised, preoperative exercise and education program compared to usual care alone in reducing the proportion of patients with postoperative in-hospital complications. The secondary aims are to investigate the effectiveness of the preoperative intervention on reducing the length of intensive care unit and hospital stay, improving quality of life and morbidity, and reducing costs. Methods This is a multi-centre, assessor-blinded, pragmatic, comparative, randomised controlled trial. A total of 172 patients undergoing pelvic exenteration, cytoreductive surgery, oesophagectomy, hepatectomy, gastrectomy or pancreatectomy will be recruited. Participants will be randomly allocated to prehabilitation with a preoperative exercise and education program (intervention group), delivered over 4 to 8 weeks before surgery by community physiotherapists/exercise physiologists, or usual care alone (control group). The intervention will comprise 12 to 24 individualised, progressive exercise sessions (including aerobic/anaerobic, resistance, and respiratory exercises), recommendations of home exercises (16 to 32 sessions), and daily incidental physical activity advice. Outcome measures will be collected at baseline, the week prior to surgery, during the hospital stay, and on the day of discharge from hospital, and 1 month and 1 months postoperatively. The primary outcome will be the development of in-hospital complications. Secondary outcomes include the length of intensive care unit and hospital stay, quality of life, postoperative morbidity and costs. Discussion The successful completion of this trial will provide robust and high-quality evidence on the efficacy of a preoperative community- and home-based exercise and education intervention on important postoperative outcomes of patients undergoing major gastrointestinal cancer surgery

Regulation of executive remuneration: an empirical study of the first three years of a 'disclosure and voting' regime in Australia and the UK

© 2010 Dr. Kym Maree SheehanLegislation by the UK government in 2002 and the Australian government in 2004 sought to improve board accountability for executive remuneration practices in listed companies. The thesis examines whether the remuneration report plus an advisory vote were effective in achieving this and other government policy aims (such as reducing excessive remuneration and aligning pay with performance). The thesis focuses upon the initial three years of this regime in the UK (2003-2005) and Australia (2005/06-2007/08). Part I of the thesis reviews three theories of motivation from the human resource management literature, together with two derivatives of agency theory (optimal contract and the managerial power thesis) to justify executive remuneration practices and the need for it to be regulated. Drawing upon the concept of ‘regulatory space’ and Julia Black's writings on rule dimension and regulatory conversation, the thesis presents a conceptual model of the regulatory framework for executive remuneration: the regulated remuneration cycle consisting of four activities (remuneration practice, disclosure, engagement and voting). Close analysis of the rule types, regulators and regulatees within this regulated remuneration cycle demonstrates that most of the rules found in the cycle take the form of statements of best practice, or other kinds of ‘soft law’, rather than legislation. Thus enforcement of good remuneration practices does not rely upon legal sanctions. The enforcement pyramid for remuneration practice confirms that most of the enforcement strategies for remuneration practice belong to shareholders. However, the regulated remuneration cycle exposes the three roles that shareholders play within this regulatory space: a rule-maker for executive remuneration practice, an active engager of remuneration committees and a routine voter on remuneration-related resolutions. Part II presents qualitative and quantitative empirical evidence of the operation of the remuneration report and advisory vote in both jurisdictions. It analyses remuneration reports and voting results for a sample of companies from the FTSE 100 and the S&P/ASX 200 for the first three years. It supplements this publicly available information with interview evidence from remuneration committees and their consultants, institutional investors and institutional representative organisations. By analysing the rules for each of the four activities in light of the evidence of how they work in practice, it demonstrates the challenges facing remuneration committees and institutional investors in working within the regulated remuneration cycle. Using the advisory vote as a proxy for shareholder outrage, it demonstrates the effect that the vote had on remuneration practice over the first three years of its operation was not identical in the UK and Australia. Part III concludes the thesis by presenting six findings on the operation of the regulatory initiatives of the remuneration report and advisory vote. These reforms were only partially successful in improving board accountability and unsuccessful in reducing excessive remuneration over the first three years of its operation. The implications of these findings for the regulatory reforms enacted in response to the global financial crisis are noted

Seven: the Corporations Act, corporate governance and termination payments to senior employees

This paper presents an empirical analysis of the termination payments contemplated by the service contracts of the managing directors of ASX50 companies. It uses real remuneration data from those companies’ 2005 annual reports to test the operation of the relevant provisions in the Corporations Act 2001 (Cth). It also compares the scheme of the Act with key corporate governance guidelines from the ASX and the Australian Council of Super Investors, Inc. The paper shows, among other things, that the Act would allow companies to make far higher termination payments without shareholder approval than is their present practice. It also highlights the importance of share-based payments as an element of executive remuneration generally, and in the context of termination in particular

Share-based remuneration and termination payments to company directors: what are the rules?

An analysis of how the provisions of the Corporations Act 2001 (Cth) are intended to operate to control termination payments to company directors, and whether the scheme of the Act can work effectively to regulate the widespread practice of share-based remuneration. The authors argue that most of the value of share-based remuneration is likely to fall outside the scheme of the Act. This would seem to allow companies to make discretionary decisions about executive termination payments that are inconsistent with the intention of the Act

SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females

Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms. SPEN encodes a transcriptional repressor commonly deleted in proximal del1p36 syndrome and is located centromeric to the proximal 1p36 critical region. Here, we used clinical data from 34 individuals with truncating variants in SPEN to define a neurodevelopmental disorder presenting with features that overlap considerably with those of proximal del1p36 syndrome. The clinical profile of this disease includes developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI, especially in females. SPEN also emerges as a relevant gene for del1p36 syndrome by co-expression analyses. Finally, we show that haploinsufficiency of SPEN is associated with a distinctive DNA methylation episignature of the X chromosome in affected females, providing further evidence of a specific contribution of the protein to the epigenetic control of this chromosome, and a paradigm of an X chromosome-specific episignature that classifies syndromic traits. We conclude that SPEN is required for multiple developmental processes and SPEN haploinsufficiency is a major contributor to a disorder associated with deletions centromeric to the previously established 1p36 critical regions

SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females

Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms. SPEN encodes a transcriptional repressor commonly deleted in proximal del1p36 syndrome and is located centromeric to the proximal 1p36 critical region. Here, we used clinical data from 34 individuals with truncating variants in SPEN to define a neurodevelopmental disorder presenting with features that overlap considerably with those of proximal del1p36 syndrome. The clinical profile of this disease includes developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI, especially in females. SPEN also emerges as a relevant gene for del1p36 syndrome by co-expression analyses. Finally, we show that haploinsufficiency of SPEN is associated with a distinctive DNA methylation episignature of the X chromosome in affected females, providing further evidence of a specific contribution of the protein to the epigenetic control of this chromosome, and a paradigm of an X chromosome-specific episignature that classifies syndromic traits. We conclude that SPEN is required for multiple developmental processes and SPEN haploinsufficiency is a major contributor to a disorder associated with deletions centromeric to the previously established 1p36 critical regions.The article is available via Open Access. Click on the 'Additional link' above to access the full-text.Published version, accepted version (6 month embargo), submitted versio