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We compared blue light flexible cystoscopy with white light flexible cystoscopy for the detection of bladder cancer during surveillance.Patients at high risk for recurrence received hexaminolevulinate intravesically before white light flexible cystoscopy and randomization to blue light flexible cystoscopy. All suspicious lesions were documented. Patients with suspicious lesions were referred to the operating room for repeat white and blue light cystoscopy. All suspected lesions were biopsied or resected and specimens were examined by an independent pathology consensus panel. The primary study end point was the proportion of patients with histologically confirmed malignancy detected only with blue light flexible cystoscopy. Additional end points were the false-positive rate, carcinoma in situ detection and additional tumors detected only with blue light cystoscopy.Following surveillance 103 of the 304 patients were referred, including 63 with confirmed malignancy, of whom 26 had carcinoma in situ. In 13 of the 63 patients (20.6%, 95% CI 11.5-32.7) recurrence was seen only with blue light flexible cystoscopy (p0.0001). Five of these cases were confirmed as carcinoma in situ. Operating room examination confirmed carcinoma in situ in 26 of 63 patients (41%), which was detected only with blue light cystoscopy in 9 of the 26 (34.6%, 95% CI 17.2-55.7, p0.0001). Blue light cystoscopy identified additional malignant lesions in 29 of the 63 patients (46%). The false-positive rate was 9.1% for white and blue light cystoscopy. None of the 12 adverse events during surveillance were serious.Office based blue light flexible cystoscopy significantly improves the detection of patients with recurrent bladder cancer and it is safe when used for surveillance. Blue light cystoscopy in the operating room significantly improves the detection of carcinoma in situ and detects lesions that are missed with white light cystoscopy.

Sudden cardiac arrest (SCA) is a leading cause of death in the United States. Despite return of spontaneous circulation, patients die due to post-SCA syndrome that includes myocardial dysfunction, brain injury, impaired metabolism, and inflammation. No medications improve SCA survival. Our prior work suggests that optimal Akt activation is critical for cooling protection and SCA recovery. Here, we investigate a small inhibitor of PTEN, an Akt-related phosphatase present in heart and brain, as a potential therapy in improving cardiac and neurological recovery after SCA. Anesthetized adult female wild-type C57BL/6 mice were randomized to pretreatment of VO-OHpic (VO) 30 min before SCA or vehicle control. Mice underwent 8 min of KCl-induced asystolic arrest followed by CPR. Resuscitated animals were hemodynamically monitored for 2 h and observed for 72 h. Outcomes included heart pressure-volume loops, energetics (phosphocreatine and ATP from 31P NMR), protein phosphorylation of Akt, GSK3β, pyruvate dehydrogenase (PDH) and phospholamban, circulating inflammatory cytokines, plasma lactate, and glucose as measures of systemic metabolic recovery. VO reduced deterioration of left ventricular maximum pressure, maximum rate of change in the left ventricular pressure, and Petco2 and improved 72 h neurological intact survival (50% vs. 10%; P < 0.05). It reduced plasma lactate, glucose, IL-1β, and Pre-B cell colony enhancing factor, while increasing IL-10. VO increased phosphorylation of Akt and GSK3β in both heart and brain, and cardiac phospholamban phosphorylation while reducing p-PDH. Moreover, VO improved cardiac bioenergetic recovery. We concluded that pharmacologic PTEN inhibition enhances Akt activation, improving metabolic, cardiovascular, and neurologic recovery with increased survival after SCA. PTEN inhibitors may be a novel pharmacologic strategy for treating SCA.

Purpose – The purpose of this paper is to focus on the potential role that performance management could play in enabling employees’ adaptability to change and, therefore, successful change implementation. Design/methodology/approach – This research adopted a qualitative case study research design, focussed on seven case studies within the Australian Public Service (APS). This study utilized documentary analysis, semi-structured individual and group interviews. Findings – The findings of this research demonstrate that adaptability to change is integral for high performance; however, the constant change faced by many public servants is disruptive. The authors posit that applying a performance framework developed by Blackman et al. (2013a, b) to change implementation will help overcome, or at least mitigate, these issues. The authors argue that applying this framework will: enable adaptability to change; and provide an ongoing management function that enables change to occur. Research limitations/implications – This research has been limited to seven organizations within the APS, yet it does reveal interesting implications in terms of the apparent role of performance management in both developing change capacity and supporting espoused outcomes. Practical implications – This research identifies the potential role that performance management can play in supporting effective change implementation through enabling employees to cope better with the change through enabling clarity, purpose and alignment with the organizational direction. Originality/value – The originality of this paper stems from the synthesis of different strands of literature, specifically high performance, performance management and change management, and empirical research in the public sector to provide a new way of looking at performance management as a change enabler.

The Workplace Remuneration Arrangement agreed between the Australian Government and the Australian Defence Force (ADF) provides for a 4.5% pay over 3 years for ADF personnel. This article makes use of the concept of the psychological contract to argue that this pay deal represents a breach of the Australian Government's obligations towards ADF personnel that is likely to have unintended consequences for their long-term commitment to their ADF careers.

A novel approach towards the production of diverse sets of diaminopyrimidines through sequential S N Ar reactions is reported. The readily prepared 2-chloro-4-tetrafluorophenoxypyrymidine reacts regioselectively with amines at the C-2 position. The tetrafluorophenoxy at C-4 can then be replaced with amines in a second S N Ar to afford easy access to a different and complementary set of diaminopyrimidines. The broad utility of this ‘C-2 then C-4’ two-step sequence has been demonstrated with a range of aromatic and aliphatic amines.

We present a time series of data for temperature, salinity, nitrate, and carbonate chemistry from September 2011 to July 2013 at the University of Washington's Friday Harbor Laboratories. Samples were collected at the Friday Harbor dock and pump house. Seawater conditions at Friday Harbor were high nitrate-low chlorophyll, with average nitrate and pCO2 concentrations of ∼ 25 ± 5 μmol L−1 and ∼ 700 ± 103 μatm (pH 7.80 ± 0.06). Transient decreases in surface water nitrate and pCO2 corresponded with the timing of a spring bloom (April through June). The high nitrate and pCO2 originate from the high values for these parameters in the source waters to the Salish Sea from the California Undercurrent (CU). These properties are due to natural aerobic respiration in the region where the CU originates, which is the oxygen minimum zone in the eastern tropical North Pacific. Alkalinity varies little so the increase in pCO2 is due to inputs of dissolved inorganic carbon (DIC). This increase in DIC can come from both natural aerobic respiration within the ocean and input of anthropogenic CO2 from the atmosphere when the water was last at the sea surface. We calculated that the anthropogenic “ocean acidification” contribution to DIC in the source waters of the CU was 36 μmol L−1. This contribution ranged from 13% to 22% of the total increase in DIC, depending on which stoichiometry was used for C/O2 ratio (Redfield vs. Hedges). The remaining increase in DIC was due to natural aerobic respiration.

A novel synthetic route to 2,4-functionalized pyrimidines is reported. The approach uses 2-chloro-4-tetrafluorophenoxypyrimidine, that enables sequential palladium catalyzed functionalization at the pyrimidine C-2 position, followed by S N Ar displacement with diverse amines at C-4 . The broad utility of this ‘ C-2 then C-4 ’ functionalization sequence has been demonstrated with a range of cross-coupling partners and amines.

Background. Recovery of arm function after stroke is often incomplete. An improved understanding of brain structure–motor behavior relationships is needed for the development of novel and targeted rehabilitation interventions. Objective. To examine the relationship between skilled reach performance and the integrity of two putative white matter motor pathways, corticospinal tract and corpus callosum, after stroke. Methods. Eleven individuals with chronic stroke (poststroke duration, mean 62.5 ± 42.4 months) and mild motor impairment (upper extremity Fugl-Meyer score, mean 54.2 ± 7.6) reached to six targets presented at three distances and two directions. Fractional anisotropy (FA) obtained from diffusion tensor imaging was used to determine the structural integrity of the corticospinal tract and the corpus callosum. Results. Overall reach performance was decreased in the paretic arm compared with the nonparetic arm. While FA was decreased in the ipsilesional corticospinal tract, FA in the corticospinal tract did not correlate with variability in reach performance between individuals. Instead, FA in the premotor section of the corpus callosum correlated with reach performance; individuals with higher FA in premotor corpus callosum tended to reach faster with both the paretic and nonparetic arms. Conclusions. The structural connections between the two premotor and supplemental cortices that traverse the premotor corpus callosum may play an important role in supporting motor control and could become a target for interventions aimed at improved arm function in this population.

A fundamental contribution of consumer behavior research is to help marketing scholars develop an understanding of how people think about and express their preferences. In this article we find that two commonly used preference elicitation procedures, willingness to pay (WTP) and choice, are consistently associated with different expressed preferences. Specifically, choices are associated with a relatively greater preference for hedonic goods, while WTP is associated with a relatively greater preference for utilitarian goods. We find that this is caused, in part, by the greater reliance on deliberation in determining WTP values, while preferences in choices are determined by an affect heuristic. Unlike other choice and WTP preference reversals, we find that this effect is not caused by mechanical determinants such as scale compatibility, as the effect persists with continuous scale measures that rely on affect and with choice-based scale measures that rely on determining valuation.

Purpose Long chain fatty acid (LCFA) oxidation measurements in the intact heart from 13C-NMR rely on detection of 13C-enriched glutamate. However, progressive increases in overlapping resonance signal from LCFA can confound detection of the glutamate 4-carbon (GLU-C4) signal. We evaluated alternative 13C labeling for exogenous LCFA and developed a simple scheme to distinguish kinetics of LCFA uptake and storage from oxidation. Methods Sequential 13C-NMR spectra were acquired from isolated rat hearts perfused with 13C LCFA and glucose. Spectra were evaluated from hearts supplied: U 13C LCFA, [2,4,6,8,10,12,14,16-13C8] palmitate, [2,4,6,8,10,12,14,16,18-13C9] oleate, [4,6,8,10,12,14,16-13C7] palmitate, or [4,6,8,10,12,14,16,18-13C8] oleate. Results 13C signal reflected the progressive enrichment at 34.6 ppm from GLU-C4, confounded by additional signal with distinct kinetics attributed to 13C-enriched LCFA 2-carbon (34.0 ppm). Excluding 13C at the 2-carbon of both palmitate and oleate eliminated signal overlap and enabled detection of the exponential enrichment of GLU-C4 for assessing LCFA oxidation. Conclusion Eliminating enrichment at the 2-carbon of 13C LCFA resolved confounding kinetics between GLU-C4 and LCFA 2-carbon signals. With this enrichment scheme, oxidation of LCFA, the primary fuel for cardiac ATP synthesis, can now be more consistently examined in whole organs with dynamic mode, proton-decoupled 13C-NMR. Magn Reson Med 74:330–335, 2015. © 2014 Wiley Periodicals, Inc.

This paper is concerned with how Appraisal Analysis (Martin and White, 2005) can be used to shed light on the identity that writers/speakers assume when they write/speak, and on the identity these text producers assign to the other voices that participate in the text. Further, we present a methodology of corpus annotation which best supports this approach to identity. The paper shows how Appraisal annotation can be used to reveal the social values held by a writer (and assigned to the other voices introduced into the text) and the affiliations of the writer.

An integral component of public management reform in Korea has been e-government, a field in which Korea has been a pioneer and in which it is the world leader. This article examines the Korean model of public management reform in the context of the developmental state and democratisation to describe and explain the emergence and expansion of e-government practices. The growth of e-government is tracked and the crucial role of the Ministry of Public Administration and Security delineated. Also covered are Government for Citizens initiatives, the provision of particular services, the mushrooming use of smart phones and emerging patterns of citizen participation, especially as related to local-level governance. The article demonstrates how much can be achieved in e-government and provides a model from which other countries can choose appropriate practices.

This paper examines performance evaluation outcomes for middle managers in the garment sector in Sri Lanka and seeks to explain variations in levels of job involvement and perceptions of organizational support. Some 155 middle managers across three firms were segregated into high- and low-performing groups. High-performing managers tended to have higher perceptions of organizational support, resulting in a social exchange relationship with their employer, and expressed higher job satisfaction and lower turnover intentions. Managers assessed as low performers experienced more negative perceptions of organizational support, lower job satisfaction and an economic exchange relationship with their employer. Significantly, for both high and low performers these outcomes were moderated by job involvement. These findings highlight the need for organizations to pay careful attention to the factors influencing job involvement and perceived organizational support. The paper concludes with a discussion on the practic...

This article traces the role of the state in developmental theory and practice, paying particular attention to public sector management. The early orthodoxy of modernisation theory put the state at the centre of development, giving it prime responsibility for generating development. Realisations of the shortcomings of modernisation theory and disappointment with its results led to the rise of neoliberal approaches in development thinking and action, with a focus on the shrinking state. However, in turn, the efficacy of neoliberalism has been questioned, and its human toll has been critiqued. Coupled with evidence of the success of the East Asian developmental states, the result has been a rethinking of the state and a new acknowledgment of its central role in development. Strong institutions and efficient, effective and responsive public sector management have been identified as key ingredients of capable states that made development happen. In outlining this trajectory, the article introduces the case studies that comprise this symposium.

The Australian Labor government’s recognition of collective bargaining under its Fair Work Act 2009, and its efficiency drive from late 2011 across the Australian Public Service (APS), presented the Community and Public Sector Union (CPSU) with an opportunity to explore means of union renewal following a decade of conservative governments focused on union exclusion. An expanding budget deficit in 2011 placed considerable financial constraints on Australian government revenue. The Labor government increased the annual “efficiency dividend”, or across the board cuts in funding, from 1.5 per cent in May 2011 to 4 per cent in November 2011 as it attempted to achieve a budget surplus. This placed considerable pressure on agency management to remain within tight constraints on wage increases and to find budget savings, resulting in growing job losses from 2011. There was also considerable central oversight over bargaining outcomes throughout this bargaining round, with the Australian Public Service Commission (APSC) involved at all stages of the agreement-making process, to the frustration of many agencies and the CPSU. Nevertheless, throughout the 2011-12 bargaining round, the CPSU worked with its members to develop creative forms of industrial action, such as one minute stoppages in the Defence department. The union also mobilized an overwhelming majority of APS employees to vote “no” in response to initial offers put by agency managements. In addition, the CPSU focused on winning bargaining concessions in politically sensitive government agencies and then flowing these concessions to other agencies. Typical of this approach were the agreements reached in the Immigration department and Customs agency. Union recruitment activities over 2011 resulted in a substantial rise in membership and enhanced communications with members through workplace meetings, telephone and internet communications, and emails. Such union initiatives highlight the potential for enhanced union capacities and mobilization during a time of growing austerity., Le Community and Public Sector Union (CPSU) australien a trouvé dans les politiques du gouvernement travailliste un tremplin pour enclencher un mouvement de renouvellement syndical. Deux facteurs contextuels ont contribué à cet essor. D’une part, le Fair Work Act de 2009 a redonné aux organisations syndicales un droit de cité dans les lieux de travail en favorisant la négociation collective comme méthode de détermination des conditions de travail. D’autre part, cet élan favorable a trouvé une impulsion dans les politiques d’austérité mises en oeuvre par le gouvernement travailliste afin de mater le déficit budgétaire provoqué par la crise financière de 2008. Le gouvernement travailliste a d’abord exigé des compressions des dépenses de 1,5 % pour ensuite les hausser à 4 % en novembre 2011. Le gouvernement fédéral a alors donné à la Australian Public Service Commission le mandat de superviser les négociations salariales de 2011 en même temps que diverses mesures d’austérité se soldaient par des coupures de postes au sein de la fonction publique fédérale australienne. Dans ce contexte, le CPSU a développé des stratégies innovatrices visant à faire pression sur les directions des agences et sur le gouvernement central. Cet article documente plusieurs de ces actions dans le but d’évaluer dans quelle mesure elles ont contribué au renouvellement de l’action syndicale. L’analyse des matériaux suggère que ces actions ont contribué à faire de la campagne de recrutement de nouveaux membres mise en oeuvre en 2011 un vif succès. L’utilisation des nouvelles technologies de communication, l’organisation de rencontres avec les membres sur les lieux de travail et des moyens de pression novateurs ont permis de rehausser les capacités d’action de ce syndicat. Le cas étudié démontre que même dans un contexte d’austérité budgétaire, les organisations syndicales peuvent améliorer leurs moyens d’action et de mobilisation., La Community and Public Sector Union (CPSU) australiano ha encontrado en las políticas del gobierno laboralista un trampolín para iniciar un movimiento de renovación sindical. Estos factores contextuales han contribuido a este desarrollo. De un lado, el Fair Work Act de 2009 ha devuelto a las organizaciones sindicales un derecho de ciudadanía en los lugares de trabajo favoreciendo así la negociación colectiva como método de determinación de las condiciones de trabajo. De otro lado, este impulso favorable ha encontrado un apoyo en las políticas de austeridad puestas en obra por el gobierno laboralista con el fin de controlar el déficit presupuestal provocado por la crisis financiera de 2008. El gobierno laboralista ha primero exigido la compresión de 1,5% de los gastos para luego alzarlos de 4% noviembre 2011. Luego, el gobierno federal ha dado a la Australian Public Service Commision el mandato de supervisar las negociaciones salariales de 2011 al mismo tiempo que diversas medidas de austeridad se tradujeron en supresión de puestos dentro de la función pública federal australiana. En este contexto, la CPSU ha desarrollado estrategias innovadoras con miras a hacer presiones sobre las direcciones de agencias y sobre el gobierno central. Este artículo documenta varias de estas acciones con el objetivo de evaluar en qué medida estas han contribuido a la renovación de la acción sindical. El análisis de los materiales sugiere que estas acciones han contribuido al éxito rotundo de la campana de reclutamiento de nuevos miembros realizada en 2011. La utilización de nuevas tecnologías de comunicación, la organización de encuentros con los miembros en los lugares de trabajo y los medios de presión innovadores han permitido de realzar las capacidades de acción de este sindicato. El caso estudiado demuestra que incluso en un contexto de austeridad presupuestal, las organizaciones sindicales pueden mejorar sus medios de acción y de movilización.

Background— Reduced fat oxidation in hypertrophied hearts coincides with a shift of carnitine palmitoyl transferase I from muscle to increased liver isoforms. Acutely increased carnitine palmitoyl transferase I in normal rodent hearts has been shown to recapitulate the reduced fat oxidation and elevated atrial natriuretic peptide message of cardiac hypertrophy. Methods and Results— Because of the potential for reduced fat oxidation to affect cardiac atrial natriuretic peptide, and thus, induce adipose lipolysis, we studied peripheral and systemic metabolism in male C57BL/6 mice model of transverse aortic constriction in which left ventricular hypertrophy occurred by 2 weeks without functional decline until 16 weeks (ejection fraction, −45.6%; fractional shortening, −22.6%). We report the first evidence for initially improved glucose tolerance and insulin sensitivity in response to 2 weeks transverse aortic constriction versus sham, linked to enhanced insulin signaling in liver and visceral adipose tissue (epididymal white adipose tissue [WAT]), reduced WAT inflammation, elevated adiponectin, mulitilocular subcutaneous adipose tissue (inguinal WAT) with upregulated oxidative/thermogenic gene expression, and downregulated lipolysis and lipogenesis genes in epididymal WAT. By 6 weeks transverse aortic constriction, the metabolic profile reversed with impaired insulin sensitivity and glucose tolerance, reduced insulin signaling in liver, epididymal WAT and heart, and downregulation of oxidative enzymes in brown adipose tissue and oxidative and lipogenic genes in inguinal WAT. Conclusions— Changes in insulin signaling, circulating natriuretic peptides and adipokines, and varied expression of adipose genes associated with altered insulin response/glucose handling and thermogenesis occurred prior to any functional decline in transverse aortic constriction hearts. The findings demonstrate multiphasic responses in extracardiac metabolism to pathogenic cardiac stress, with early iWAT browning providing potential metabolic benefits.

2,4-Substituted pyrimidines are prepared by C-2 functionalization of 2-chloro-4-tetrafluorophenoxypyrimidine (I) by cross-coupling reactions followed by SNAr displacement at C-4 position with a variety of amines.

Several previous studies indicated that for optimal uptake by the brain, docosahexaenoic acid (DHA) should be present as phospholipid in the plasma. However most of dietary DHA is absorbed as triacylglycerol (TAG) because it is released as free fatty acid during digestion of either TAG-DHA (fish oil) or sn-2-DHA phospholipid (krill oil), and subsequently incorporated into TAG of chylomicrons. We tested the hypothesis that the absorption of DHA as phospholipid can be increased if it is present in the sn-1 position of dietary phospholipid or in lysophosphatidylcholine (LPC), because it would escape the hydrolysis by pancreatic phospholipase A2. We infused micelle containing the DHA either as LPC or as free acid, into the duodenum of lymph cannulated rats, and analyzed the chylomicrons and HDL of the lymph for the DHA-containing lipids. The results show that while the total amount of DHA absorbed was comparable from the two types of micelle, the percentage of DHA recovered in lymph phospholipids was 5 times greater with LPC-DHA, compared to free DHA. Furthermore, the amount of DHA recovered in lymph HDL was increased by 2-fold when LPC-DHA micelle was infused. These results could potentially lead to a novel strategy to increase brain DHA levels through the diet.

The synthesis of pyridines bearing multiple ring fusions poses a considerable challenge for organic chemists. To address this problem, we describe the synthesis of a small library of pyrido[3,4-b]indoles via an efficient, five-step sequence. The key transformation is a Rh(I)-catalyzed [2 + 2 + 2] cyclization that forms three rings in one reaction flask. Our method is high yielding, accommodates a variety of functional groups, and suffers no entropic costs as ring size increases.

Background Appropriate use criteria (AUC) for cardiac stress tests address concerns about utilization growth and patient safety. We systematically reviewed studies of appropriateness, including within physician specialties; evaluated trends over time and in response to AUC updates; and characterized leading indications for inappropriate/rarely appropriate testing. Methods We searched PubMed (2005–2015) for English-language articles reporting stress echocardiography or myocardial perfusion imaging (MPI) appropriateness. Data were pooled using random-effects meta-analysis and meta-regression. Results Thirty-four publications of 41,578 patients were included, primarily from academic centers. Stress echocardiography appropriate testing rates were 53.0% (95% CI, 45.3%–60.7%) and 50.9% (42.6%–59.2%) and inappropriate/rarely appropriate rates were 19.1% (11.4%–26.8%) and 28.4% (23.9%–32.8%) using 2008 and 2011 AUC, respectively. Stress MPI appropriate testing rates were 71.1% (64.5%–77.7%) and 72.0% (67.6%–76.3%) and inappropriate/rarely appropriate rates were 10.7% (7.2%–14.2%) and 15.7% (12.4%–19.1%) using 2005 and 2009 AUC, respectively. There was no significant temporal trend toward rising rates of appropriateness for stress echocardiography or MPI. Unclassified stress echocardiograms fell by 79% (p = 0.04) with updated AUC. There were no differences between cardiac specialists and internists. Conclusions Rates of appropriate use tend to be lower for stress echocardiography compared to MPI, and updated AUC reduced unclassified stress echocardiograms. There is no conclusive evidence that AUC improved appropriate use over time. Further research is needed to determine if integration of appropriateness guidelines in academic and community settings is an effective approach to optimizing inappropriate/rarely appropriate use of stress testing and its associated costs and patient harms.

This study explores employees’ perceptions of organisational support, commitment, job satisfaction and turnover intentions in Sri Lanka Telecom (SLT). Organisational support involves the provision of valued financial benefits along with employees’ perceptions of support from supervisors and co-workers, and procedural fairness in decision-making. We found strong evidence that high levels of organisational support lead to employee reciprocity via increased affective commitment and job satisfaction and reduced turnover intentions. We also found evidence, albeit weaker, of a positive relationship between economic exchange and continuance commitment, where employees may be dissatisfied but stay because they have too much invested in firm specific knowledge and skills. The firm provided above average compensation and benefits and with limited alternative job opportunities in the formal economy in Sri Lanka the costs of leaving the organisation are likely to have outweighed the costs of staying.

This study begins with a brief theoretical discussion of the defining features of new public management (NPM) and its employment relations implications. This is followed by analyses of the managerial and union strategies through which change was effected, resisted and negotiated in Australia and New Zealand. The discussion contrasts the approaches to regulating employment relations that waxed and waned under a succession of Labor and Coalition governments in Australia and Labour and National governments in New Zealand. The conclusion is one of survival in both countries, both of elements of NPM and of public sector unionism.

This paper examines the privatisation of Sydney Airport and the regime of ‘light-handed’ monitoring of service quality and airport charges that followed the sale in 2002. The arguments for privatisation are reviewed, in particular the need for increased competition and/or appropriate regulation where a former public monopoly, such as Sydney Airport, is sold. The aftermath of the privatisation of the airport has led to complaints by the major airlines and consumers of ever increasing charges for use of the airfield and for car parking and other services. This highlights that the ‘light-handed’ monitoring regime has not constrained the airport’s ability to charge monopoly rents. The aftermath of privatisation has resulted in labour shedding, outsourcing and a focus on cost minimisation by the airport’s management.

Whether voluntary or mandatory in nature, most recent corporate governance codes of best practice assume that board structural independence, and the application by boards of outcome-based incentive plans, are important boundary conditions for the enforcement of Chief Executive Officer (CEO) pay-for-firm-performance; that is, for optimal contracting between owners and executive agents. We test this logic on a large Australian sample using a system Generalized Method of Moments (GMM) approach to dynamic panel data estimation. We find that Australian boards exhibiting best practice structural arrangements – those chaired by non-executives and dominated by non-executive directors at the full board and compensation committee levels – are no more adept at enforcing CEO pay-for-firm-performance than are executive-dominated boards. These findings suggest that policy makers' faith in incentive plans and the moderating influence of structural independence per se may be misplaced. Our findings also hold significant implications for corporate governance theory. Specifically, the findings lend further support to a contingency-based understanding of board composition, reward choice and monitoring; an approach integrating the insights afforded by behavioural approaches to Agency Theory and by social-cognitive and institutional understandings of director outlook, decision-making and behaviour.

DNA-damaging agents are among the most frequently used anticancer drugs. However, they provide only modest benefit in most cancers. This may be attributed to a genome maintenance network, the DNA damage response (DDR), that recognizes and repairs damaged DNA. ATR is a major regulator of the DDR and an attractive anticancer target. Herein, we describe the discovery of a series of aminopyrazines with potent and selective ATR inhibition. Compound 45 inhibits ATR with a K(i) of 6 nM, shows >600-fold selectivity over related kinases ATM or DNA-PK, and blocks ATR signaling in cells with an IC(50) of 0.42 μM. Using this compound, we show that ATR inhibition markedly enhances death induced by DNA-damaging agents in certain cancers but not normal cells. This differential response between cancer and normal cells highlights the great potential for ATR inhibition as a novel mechanism to dramatically increase the efficacy of many established drugs and ionizing radiation.

Municipal water demand has declined over the past several decades in many large cities in the western United States. The same is true in Clovis, New Mexico, which is a small town in arid eastern New Mexico, whose sole water source is from the dwindling southern Ogallala Aquifer. Using premises-level monthly panel data from 2006 to 2015 combined with climate data and additional controls, we apply a fixed effects instrumental variable approach to estimate municipal water demand. Results indicate that utility-controlled actions such as price increases and rebates for xeriscaping and water saving technology have contributed to the decline. Overall water demand was found to be price inelastic and in the neighborhood of [Formula: see text]0.50; however, premises receiving toilet and washing machine rebates were relatively more price inelastic and premises receiving landscaping rebates were more price elastic, though still inelastic. In addition, the average premises receiving its first toilet rebate reduced water use by 8.4%, washing machine rebates lowered use by 9.2%, and the average landscaping rebate reduced water use by less than 5.0%. From the utility’s perspective, and assuming a 5.0% discount rate, levelized cost analysis indicates that toilet rebates are 34% more cost effective than washing machine rebates and nearly 800% more cost effective than landscaping rebates over their respective lives per volume of water conserved. While this research focuses on Clovis, estimation results can be leveraged by other small to mid-sized cities experiencing declining supplies, confronting climate change, and with little opportunity for near-term supply enhancement.

Objectives This study sought to evaluate the prevalence, risk factors, outcomes, and predictors of mortality of retroperitoneal hematoma (RPH) following percutaneous coronary intervention. Background Retroperitoneal hematoma is a serious complication of invasive cardiovascular procedures. Methods The study sample included 112,340 consecutive patients undergoing percutaneous coronary intervention in a large, multicenter registry between October 2002 and December 2007. End points evaluated included the development of RPH and mortality. Results Retroperitoneal hematoma occurred in 482 (0.4%) patients. Of these, 92.3% were treated medically and 7.7% underwent surgical repair. Female sex, body surface area Conclusions Retroperitoneal hematoma is an uncommon complication of contemporary percutaneous coronary intervention associated with high morbidity and mortality. The identification of risk factors for the development of RPH could lead to modification of procedure strategies aimed toward reducing its incidence.

Rationale : Long chain fatty acids (LCFAs) are the preferred substrate for energy provision in hearts. However, the contribution of endogenous triacylglyceride (TAG) turnover to LCFA oxidation and the overall dependence of mitochondrial oxidation on endogenous lipid is largely unstudied. Objective : We sought to determine the role of TAG turnover in supporting LCFA oxidation and the influence of the lipid-activated nuclear receptor, proliferator-activated receptor (PPAR)α, on this balance. Methods and Results : Palmitoyl turnover within TAG and palmitate oxidation rates were quantified in isolated hearts, from normal mice (nontransgenic) and mice with cardiac-specific overexpression of PPARα (MHC-PPARα). Turnover of palmitoyl units within TAG, and thus palmitoyl-coenzyme A recycling, in nontransgenic (4.5±2.3 μmol/min per gram dry weight) was 3.75-fold faster than palmitate oxidation (1.2±0.4). This high rate of palmitoyl unit turnover indicates preferential oxidation of palmitoyl units derived from TAG in normal hearts. PPARα overexpression augmented TAG turnover 3-fold over nontransgenic hearts, despite similar fractions of acetyl-coenzyme A synthesis from palmitate and oxygen use at the same workload. Palmitoyl turnover within TAG of MHC-PPARα hearts (16.2±2.9, P O -acyltransferase 3), and lipolysis, Pnliprp1 (pancreatic lipase related protein 1). Conclusions : The role of endogenous TAG in supporting β-oxidation in the normal heart is much more dynamic than previously thought, and lipolysis provides the bulk of LCFA for oxidation. Accelerated palmitoyl turnover in TAG, attributable to chronic PPARα activation, results in near requisite oxidation of LCFAs from TAG.

The article examines the impact, in one Sri Lankan garment industry, of a management initiative devolving to line employees the responsibility for decision-making about workplace performance. At the time of the study, garment manufacturers in Sri Lanka faced increased pressure from international buyers to improve product quality and to meet stringent production delivery schedules, along with growing concerns from Western consumers regarding factory conditions and labour standards. One outcome of these pressures was increased experimentation with a range of quality management techniques to elicit workforce commitment to improved efficiency levels and higher quality standards. This study documents one experiment whereby production line operators rotated the role of production supervisor amongst themselves and accepted responsibility for minimising production bottlenecks, and for communicating data on workplace efficiency, product reject rates and absenteeism levels to other line operators. We found that workplace productivity and product quality increased over the 18-month period of the study, while levels of labour turnover and absenteeism declined. Nevertheless, the study also found that the increased role in workplace decision-making provided to employees also came with increased expectations that line employees would achieve higher production targets, improve quality and monitor workplace attendance.

The identification of a novel series of Aurora kinase inhibitors and exploitation of their SAR is described. Replacement of the initial quinazoline core with a pyrimidine scaffold and modification of substituents led to a series of very potent inhibitors of cellular proliferation. MK-0457 (VX-680) has been assessed in Phase II clinical trials in patients with treatment-refractory chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) containing the T315I mutation.

PurposeThe purpose of this paper is to develop a model to explain frontline employee absence as a form of concerted resistance in a public service welfare environment.Design/methodology/approachConflicts over absenteeism can be interpreted as a mix of formal and informal struggles over the effort bargain. Centrelink workers' use of “unplanned leave” between 2005 and 2007 involved the quasi‐collective use of a formal entitlement in a form of misbehaviour that defied management control.FindingsWhereas absenteeism is normally assumed to be a form of unorganised individual time‐theft, in this study it became a tacitly‐agreed form of collective resistance and a way of affirming collectively negotiated rights.Research limitations/implicationsThis paper explores how the toll of cost cutting and implementation of tighter welfare eligibility rules elicited collective resistance through leave taking and highlights how absenteeism can be more than an individual response of passive disengagement.Originality/valueUsing theories of resistance, the authors highlight how the case study both conforms to and departs from the received wisdom about absenteeism as an individual oppositional strategy.

Adenoviral gene transfer of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a to the hypertrophic heart in vivo has been consistently reported to lead to enhanced myocardial contractility. It is unknown if the faster skeletal muscle isoform, SERCA1, expressed in the whole heart in early failure, leads to similar improvements and whether metabolic requirements are maintained during an adrenergic challenge. In this study, Ad.cmv.SERCA1 was delivered in vivo to aortic banded and sham-operated Sprague-Dawley rat hearts. The total SERCA content increased 34%. At 48–72 h posttransfer, echocardiograms were acquired, hearts were excised and retrograded perfused, and hemodynamics were measured parallel to NMR measures of the phosphocreatine (PCr)-to-ATP ratio (PCr/ATP) and energy substrate selection at basal and high workloads (isoproterenol). In the Langendorff mode, the rate-pressure product was enhanced 27% with SERCA1 in hypertrophic hearts and 10% in shams. The adrenergic response to isoproterenol was significantly potentiated in both groups with SERCA1.31P NMR analysis of PCr/ATP revealed that the ratio remained low in the hypertrophic group with SERCA1 overexpression and was not further compromised with adrenergic challenge.13C NMR analysis revealed fat and carbohydrate oxidation were unaffected at basal with SERCA1 expression; however, there was a shift from fats to carbohydrates at higher workloads with SERCA1 in both groups. Transport of NADH-reducing equivalents into the mitochondria via the α-ketoglutamate-malate transporter was not affected by either SERCA1 overexpression or adrenergic challenge in both groups. Echocardiograms revealed an important distinction between in vivo versus ex vivo data. In contrast to previous SERCA2a studies, the echocardiogram data revealed that SERCA1 expression compromised function (fractional shortening) in the hypertrophic group. Shams were unaffected. While our ex vivo findings support much of the earlier cardiomyocyte and transgenic data, the in vivo data challenge previous reports of improved cardiac function in heart failure models after SERCA intervention.

The article examines changes in the collective regulation of employment relations in the Australian Public Service over the last three decades. While federal Labor Governments in the 1990s briefly experimented with agency bargaining before returning to a service-wide approach to wage bargaining, the Howard Coalition Government encouraged federal public sector managers to individualize employment relations through the widespread offer of Australian Workplace Agreements and non-union collective agreements. This agenda was reinforced by policy parameters overseen by the Department of Employment and Workplace Relations, which placed constraints on the flexibility available to managers to negotiate agency-specific employment arrangements. Despite concerted efforts to marginalize the role of the Community and Public Sector Union since 1996, the union has maintained approximately 70 percent collective bargaining coverage within the Australian Public Service. Nevertheless, the 2005 amendments to the Workplace Relations Act (1996) imposed further restrictions on unions' right of entry to public sector workplaces, made the taking of industrial action more difficult, and sent a clear signal to the Government's managerial agents to adopt a more hostile approach to public sector unions. This hostile environment has brought to the fore issues of union organization and effectiveness and the concomitant need to maintain union democracy and an active voice for members in union decision-making processes.

The Escherichia coli clamp loader, gamma complex (gamma(3)deltadelta'lambdapsi), catalyzes ATP-driven assembly of beta clamps onto primer-template DNA (p/tDNA), enabling processive replication. The mechanism by which gamma complex targets p/tDNA for clamp assembly is not resolved. According to previous studies, charged/polar amino acids inside the clamp loader chamber interact with the double-stranded (ds) portion of p/tDNA. We find that dsDNA, not ssDNA, can trigger a burst of ATP hydrolysis by gamma complex and clamp assembly, but only at far higher concentrations than p/tDNA. Thus, contact between gamma complex and dsDNA is necessary and sufficient, but not optimal, for the reaction, and additional contacts with p/tDNA likely facilitate its selection as the optimal substrate for clamp assembly. We investigated whether a conserved sequence-HRVW(279)QNRR--in delta subunit contributes to such interactions, since Tryptophan-279 specifically cross-links to the primer-template junction. Mutation of delta-W279 weakens gamma complex binding to p/tDNA, hampering its ability to load clamps and promote proccessive DNA replication, and additional mutations in the sequence (delta-R277, delta-R283) worsen the interaction. These data reveal a novel location in the C-terminal domain of the E. coli clamp loader that contributes to DNA binding and helps define p/tDNA as the preferred substrate for the reaction.

Objectives This study sought to assess whether the use of eptifibatide instead of abciximab is associated with a difference in outcomes of patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Background Pooled data from randomized controlled trials suggest that the use of abciximab may be associated with a survival advantage in patients undergoing primary PCI for acute STEMI. However, a large proportion of patients in the community are treated with eptifibatide, an agent that shares some but not all pharmacological properties with abciximab. Methods We evaluated the outcomes of 3,541 patients who underwent primary PCI for STEMI from October 2002 to July 2006 in a large regional consortium and who were treated with abciximab (n = 729) or with eptifibatide (n = 2,812). Results There was no difference in the incidence of in-hospital death (4.1% with abciximab vs. 3.5% with eptifibatide, p = 0.39), recurrent myocardial infarction (0.8% vs. 1.2%, p = 0.42), or stroke/transient ischemic attack (0.7% vs. 0.6%, p = 0.80). There was no difference in the need for blood transfusion (12.4% vs. 11.7%, p = 0.61), whereas there was a greater incidence of gastrointestinal bleeding with abciximab (4.8% vs. 2.8%, p = 0.01). In parsimonious risk-adjusted models, no significant difference between abciximab and eptifibatide was observed with respect to any of the outcomes measures. Conclusions Currently, eptifibatide is used as the adjunct antiplatelet agent in the majority of patients undergoing primary PCI. There is no apparent difference in early outcomes of patients treated with eptifibatide compared with patients treated with abciximab.