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In Tasmania's Little Swanport catchment there has been 12 years of diverse effort in research, planning and implementation to progress integrated catchment management (ICM), and natural resource management (NRM). Those labours provide an opportunity to reflect upon how to improve prospects for success in the application of ICM in that catchment; the lessons gained may have wider application given the national governance framework for NRM in Australia. The present study has four aims. The first aim is to present a critical analysis of the impacts of changes in the legislative, policy and administrative frameworks of NRM at national, state and local government levels. That analysis is informed by and sympathetic to the literature on adaptive management. The second aim is to elaborate upon a case study of onground initiatives at catchment and property scales in the Little Swanport catchment that embrace specific ICM and more general NRM strategies. That case study was based on qualitative research methods and especially those indebted to my ethnographic and action-research interventions as a participant researcher working in both the catchment and broader NRM policy circles in southern Tasmania. The third aim was to take insights from the critical analysis and fold them through those gained from the empirical work to gain an appreciation of how ICM is translated from policy to ground and with what effects for those involved in the process. The rationale for this three-step approach is that the Catchment Committee I have worked with was funded by the Australian Government through one of three regional NRM organisations, NRM South, to develop a whole-of-catchment and whole-ofecosystem planning model for the Little Swanport that could be applied more widely throughout the region. Therefore, I am both a subject in and student of the process reported here. Qualitative research methods allow for this dual status. Findings suggest that stakeholders ‚Äö- federal and state governments, local councils and community members alike ‚Äö- did not fully consider a number of cultural and governance parameters and practices that are imperative to multilateral land management ‚Äö- among them trust, commitment and communication. Without such qualities being consciously present and maintained, evidence suggests that ICM processes were doomed to fail. To counteract such an outcome, my fourth aim was to identify what qualities might be necessary for the successful delivery of ICM in southern Tasmania. These include genuine commitment to ICM for a determined length of time by key stakeholders, adequate resourcing to ensure the ongoing engagement of skilled locally based professional extension staff, and on occasion independent facilitators, a clearly articulated purpose for bringing stakeholders together, the creation of a framework and culture to facilitate trust, the development of a communication strategy and processes for conflict resolution. Additionally, ICM must be informed by research efforts identified by and involving local stakeholders. Realistic actions and expectations are essential ‚Äö- ones that recognise and respect the commitment and capacity for volunteers and paid staff. Finally, successful ICM requires a conscious adaptive management approach to enable a positive collaborative process, which results in behavioural change that maintains and improves the ecological, social and economic condition of the catchment in question.

In Tasmania’s Little Swanport catchment there has been 12 years of diverse effort in research, planning and implementation to progress integrated catchment management (ICM), and natural resource management (NRM). Those labours provide an opportunity to reflect upon how to improve prospects for success in the application of ICM in that catchment; the lessons gained may have wider application given the national governance framework for NRM in Australia. The present study has four aims. The first aim is to present a critical analysis of the impacts of changes in the legislative, policy and administrative frameworks of NRM at national, state and local government levels. That analysis is informed by and sympathetic to the literature on adaptive management. The second aim is to elaborate upon a case study of on-ground initiatives at catchment and property scales in the Little Swanport catchment that embrace specific ICM and more general NRM strategies. That case study was based on qualitative research methods and especially those indebted to my ethnographic and action-research interventions as a participant researcher working in both the catchment and broader NRM policy circles in southern Tasmania. The third aim was to take insights from the critical analysis and fold them through those gained from the empirical work to gain an appreciation of how ICM is translated from policy to ground and with what effects for those involved in the process. The rationale for this three step approach is the Catchment Committee I have worked with was funded by the Australian Government through one of three regional NRM organisations, NRM South, to develop a whole-of-catchment and whole-of ecosystem planning model for the Little Swanport that could be applied more widely throughout the region. Therefore, I am both a subject in and a student of the process reported here. Qualitative research methods allow for this dual status. Findings suggest that stakeholders – federal and state governments, local councils and community members alike – did not fully consider a number of cultural and governance parameters and practices that are imperative to multilateral land management – among them trust, commitment and communication. Without such qualities being conspicuously present and maintained, evidence suggests that ICM processes were doomed to fail. To counteract such an outcome, my fourth aim was to identity what qualities might be necessary for the successful delivery of the ICM in Southern Tasmania. These include genuine commitment to ICM for a determined length of time by key stake-holders, adequate resourcing to ensure the ongoing engagement of skilled locally based professional extension staff, and on occasion independent facilitators, a clearly articulated purpose for bringing stakeholder together, the creation of a framework and culture to facilitate trust, the development of a communication strategy and processes for conflict resolution. Additionally, ICM must be informed by research efforts identified by and involving local stake-holders. Realistic actions and expectations are essential – ones that recognise and respect the commitment and capacity for volunteers and paid staff. Finally, successful ICM requires a conscious adaptive management approach to enable a positive collaborative process, which results in behavioural change that maintains and improves the ecological, social and economic condition of the catchment in question.

A large body of work has linked dopaminergic signaling to learning and reward processing. It stresses the role of dopamine in reward prediction error signaling, a key neural signal that allows us to learn from past experiences, and that facilitates optimal choice behavior. Latterly, it has become clear that dopamine does not merely code prediction error size but also signals the difference between the expected value of rewards, and the value of rewards actually received, which is obtained through the integration of reward attributes such as the type, amount, probability and delay. More recent work has posited a role of dopamine in learning beyond rewards. These theories suggest that dopamine codes absolute or unsigned prediction errors, playing a key role in how the brain models associative regularities within its environment, while incorporating critical information about the reliability of those regularities. Work is emerging supporting this perspective and, it has inspired theoretical models of how certain forms of mental pathology may emerge in relation to dopamine function. Such pathology is frequently related to disturbed inferences leading to altered internal models of the environment. Thus, it is critical to understand the role of dopamine in error-related learning and inference.

Objective The objective of this study was to identify clinical predictors of motor complications (dyskinesia and motor fluctuations) of levodopa in a prospectively recruited PD cohort using longitudinal analysis. Methods An inception cohort (Oxford Discovery) of 734 patients was followed to a maximum of 10 years from diagnosis using a discrete‐time survival analysis. A subset analysis was used to validate an online dyskinesia‐risk calculator developed from the results of the Stalevo Reduction in Dyskinesia Evaluation PD trial. Results A total of 186 cases of dyskinesia and 254 cases of motor fluctuations were observed. Dyskinesia incidence increased with time (risk per 100 participants [95% confidence interval] 13 [11–16] 6.5 years from diagnosis). Motor complication predictors were grouped as medication predictors, disease predictors and patient predictors. Baseline nonmotor feature severity, low mood, anxiety, and age at symptom onset were associated with motor complications among a number of previously identified predictors. Replication of the Stalevo Reduction in Dyskinesia Evaluation PD calculator was reasonable with the area under the curve for dyskinesia risk score as a predictor of dyskinesia being 0.68 (95% confidence interval, 0.55–0.81). Conclusions This study quantifies risk of motor complications, finds consistent predictors, and demonstrates the novel finding that nonmotor features of PD, particularly low mood and anxiety, are significant risk factors for motor complications. Further validation of dyskinesia risk scores are required as well as evidence to determine if the routine use of such scores can be clinically valuable in enhancing patient care and quality of life. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Impulse control behaviours (ICBs) are a range of behaviours linked by their reward-based, repetitive natures. They can be precipitated in Parkinson's disease (PD) by dopamine replacement therapy, often with detrimental consequences for patients and caregivers. While now a well-recognised non-motor feature of treated PD, much remains unknown about the influence of risk factors, pathophysiological mechanisms, vulnerability factors for specific types of behaviour and the optimal management strategies. Imaging studies have identified structural and functional changes in striatal and prefrontal brain regions, among others. Gene association studies indicate a role for genetic predisposition to PD-ICB. Clinical observational studies have identified potential modifiable and non-modifiable risk factors. Psychological studies shed light on the neurocognitive domains implicated in PD-ICBs and identify psychosocial determinants that may perpetuate the cycle of impulsive and harm-avoidance behaviours. Based on these results, a range of pharmacological and non-pharmacological management strategies have been trialled in PD-ICBs with varying success. The purpose of this review is to update clinicians on the evidence around the pathophysiology of PD-ICB. We aim to translate our findings into an interpretable biopsychosocial model that can be applied to the clinical assessment and management of individual cases of PD-ICB.

Impact Statement: We report on the first demonstration of a low loss and tunable metamaterial based on high-temperature superconducting BSCCO. BSCCO with large superconducting energy gap is the building block of a compact, powerful, continuous and coherent THz source which has been found promising to close the THz gap. Our proposed metamaterial can be integrated with BSSCO THz emitters to improve their functionalities., We introduce a class of low-loss subwavelength resonators and report the first demonstration of a high-temperature ( Tc) superconducting Bi 2Sr2 CaCu2O 8+δ (BSCCO) terahertz (THz) metamaterial. The numerical simulations and analytical calculations are performed to study the electromagnetic response of the subwavelength BSCCO split-ring resonators (SRRs) to the incident photons with energies below the superconducting gap energy. A transition of resonance strength is observed as a dip in resonance frequency for temperatures below BSCCO Tc. To interpret the transmission spectra, resonance switching, and frequency tuning of SRRs, we calculate the temperature dependent complex permittivity and surface impedance of a 200 nm thick unpatterned slightly underdoped BSCCO thin film. We compare the resonance tunability of SRRs made of the extremely disorder superconductor (BSCCO) with metamaterials made of a weakly disorder superconductor YBa2Cu3O7 (YBCO) and show that the resonance quality and frequency tuning are comparable for these two metamaterials. Our results may be useful for THz emitters and detectors developments, for instance, by integration of SRRs with BSCCO THz emitters and microstrip antennas, the device functionalities such as polarization, emission pattern directivity, and output power could be controlled and improved.

We introduce a class of low-loss subwavelength resonators and report the first demonstration of a high-temperature (Tc) superconducting Bi2Sr2CaCu2O8+d (BSCCO) terahertz (THz) metamaterial. The numerical simulations and analytical calculations are performed to study the electromagnetic response of the subwavelength BSCCO split-ring resonators (SRRs) to the incident photons with energies below the superconducting gap energy. A transition of resonance strength is observed as a dip in resonance frequency for temperatures below BSCCO Tc. To interpret the transmission spectra, resonance switching and frequency tuning of SRRs, we calculate the temperature dependent complex permittivity and surface impedance of a 200 nm thick unpatterned slightly-underdoped BSCCO thin film. We compare the resonance tunability of SRRs made of the extremely disorder superconductor (BSCCO) with metamaterials made of a weakly disorder superconductor (YBCO) and show that the resonance quality and frequency tuning are comparable for these two metamaterials. Our results may be useful for THz emitters and detectors developments, for instance, by integration of SRRs with BSCCO THz emitters and microstrip antennas, the device functionalities such as polarization, emission pattern directivity, and output power could be controlled and improved.

For a science to become a technology, a certain level of control has to have been established over the way items are fabricated for manufacture and use. Here we first consider the challenge of making and using a LEGO(®) brick scaled down by a factor of 10(n) for n = 0-6 in each spatial dimension, i.e. from millimetres to nanometres. We consider both the manufacture and the subsequent properties of the nanobricks that pertain to their use in constructing and dismantling structures. As n increases, the ability to use fails first, to manufacture fails second and to fabricate fails last. Applied to the vast literature in nanoscience, this process emphasises the unmanufacturability of most nanoscale artefacts.

It is widely promulgated and believed that human-caused global warming comes with increases in both the intensity and frequency of extreme weather events. A survey of official weather sites and the scientific literature provides strong evidence that the first half of the 20th century had more extreme weather than the second half, when anthropogenic global warming is claimed to have been mainly responsible for observed climate change. The disconnect between real-world historical data on the 100 years’ time scale and the current predictions provides a real conundrum when any engineer tries to make a professional assessment of the real future value of any infrastructure project which aims to mitigate or adapt to climate change. What is the appropriate basis on which to make judgements when theory and data are in such disagreement?

This chapter summarizes literature on handedness, language, and cerebral asymmetry as evidenced by lesion and neuroimaging studies. The development of non-invasive techniques has allowed us to determine functional brain asymmetries even in healthy subjects. The chapter comments on the possible origin of dexterity and language lateralization, the individual differences in laterality, as well as the distribution of laterality at the population level. Human brain imaging studies indicate that Broca's area, which is located in the pars opercularis of the inferior frontal gyrus, may be part of the human mirror neuron system as well as the superior temporal sulcus and the inferior parietal lobule. The relation between handedness and language lateralization invites speculation on the underlying neural causes. Lateralization of language functions should aid the processing demands required for a full exhaustion of linguistic capacities.

Background Postoperative portal vein infusion (PVI) of 5-fluorouracil (5-FU) is a well tolerated and widely applicable treatment for colorectal cancer that might have an enormous public health impact, even if it produced survival benefits of just a few per cent. Very large trials are required to detect such differences, and the Adjuvant X-ray and 5-FU Infusion Study (AXIS) is the largest such trial yet reported. Methods Consenting patients with presumed colorectal cancer were randomized to surgery with or without 7 days of PVI (1 g 5-FU plus 5000 units heparin in 1 litre 5 per cent dextrose infused over each 24-h period). In addition, patients with rectal cancer could be randomized to radiotherapy or no radiotherapy to be given either before or after surgery. Results Between November 1989 and December 1997, 3583 patients were randomized with respect to PVI. The survival hazard ratios (95 per cent confidence interval (c.i.)) in all patients randomized and in the curatively resected subgroup (71·2 per cent of patients) were 1·00 (0·92 to 1·11) and 0·94 (0·83 to 1·06) respectively. Tests for heterogeneity suggested a greater treatment benefit for patients with colonic cancer than for patients with rectal cancer with respect to disease-free survival (hazard ratio 0·79 versus 1·03; P = 0·07), and there was a non-significant trend with respect to overall survival (hazard ratio 0·87 versus 1·03; P = 0·17). No survival benefit was seen in the 761 patients randomized with respect to radiotherapy; although not statistically significant, the impact on local recurrence rates was similar to that reported in the literature. Conclusion No overall benefit of PVI was established in AXIS when colonic and rectal cancers were considered together, but the evidence suggesting a differential treatment effect according to site of cancer in AXIS was strongly supported by a meta-analysis incorporating the previous trials. Combining the data gave hazard ratios of 0·82 and 1·00 for colonic and rectal tumours respectively (test for interaction, P = 0·024), equating to an absolute survival benefit for patients with colonic cancer of 5·8 (95 per cent c.i. 2·8 to 8·5) per cent, a level close to that seen for prolonged systemic therapy.

The pharmacological action of vitamin E on the mechanical activity of isolated guinea pig colonic smooth muscle was examined in normoxic and hypoxic conditions. In hypoxia, but not normoxia, alpha-tocopherol (1-160 microM) evoked rapid concentration-dependent contractions from the colon. This was also seen with other members of the vitamin E family, and potency measurements gave EC(50) values (microM) of 10.6 +/- 0.9 for D-alpha-tocopherol, 6.0 +/- 1.2 for D-beta-tocopherol, 7.5 +/- 0.7 for D-gamma-tocopherol, and 6.1 +/- 1.5 for D-delta-tocopherol. This order of potency for the components of the vitamin differs from previously studied bioassay systems and from their antioxidant activity. A range of potent natural and synthetic antioxidants was not active in this system. Compounds with structural similarities to the side chain of vitamin E produced similar stimulatory responses and some, like phytol, were more potent than the vitamin (EC(50): 1.0 +/- 0.2 microM), whereas ring structures related to the vitamin, like Trolox C, antagonized the stimulant responses in a concentration-dependent manner. Therefore, this model system measures, directly, vitamin E-induced responses through a mechanism that does not appear to be related to the known antioxidant capacity of these agents.

Gastrointestinal blood pool scintigraphy, using a modified in-vivo red blood cell labelling technique with technetium-99, is a new, easily performed, non-invasive procedure. It is valuable in screening patients with acute or intermittent gastrointestinal blood loss in whom duodenoscopic and sigmoidoscopic findings are unhelpful. This paper reviews the value of this scintigraphic technique over the first eight months of its use in a major teaching hospital, and compares the results with other published data. The high sensitivity of this procedure, and its ability to demonstrate gastrointestinal bleeding very strikingly, are illustrated with several examples. If used and interpreted appropriately, scintigraphy is sensitive in detecting and localizing the bleeding site, and is very helpful in indicating the optimal timing of emergency contrast angiography. The study further supports the view that scintigraphy should be the initial diagnostic imaging procedure in this group of patients, and that emergency angiography should be reserved primarily for patients in whom there is scintigraphic evidence of continuing blood loss.

In hypoxia, but not normoxia, α-tocopherol (vitamin E) acts as an agonist in guinea-pig isolated colon, producing dose-dependent increases in contractile activity. This effect is mimicked by agents, vitamin K1 and phytol, which contain a structural similarity to the phytyl side chain of α-tocopherol, but is antagonized by vitamin K3 which has a structure similar to the chromane ring of vitamin E. All of the agonist responses were blocked by atropine and potentiated by physostigmine but were unaffected by nexamethonium. However, responses to acetylcholine were not antagonized by vitamin K3 and these data suggest that α-tocopherol, phytol, vitamins K1 and K3 may be acting on a ‘hypoxia receptor’ which mediates release of acetylcholine onto muscarinic receptors.

Publisher Summary This chapter discusses the pharmacology of Vitamin E. Vitamin E (alpha-tocopherol) is still perhaps the least understood of all the body's vitamins in terms of its biological actions. In some respects, the paucity of information has fuelled a continuing interest in vitamin E, but this gap in established scientific knowledge has also generated many speculative biological roles and doubtful potential therapeutic applications. Other notable findings concerning vitamin-E-deficient animals established hepatic lesions and accumulation of lipopigment while addition of the vitamin to the diet of rabbits evoked enhanced immune function. Early studies in vitamin-E deficiency states in animals produced sufficient diverse and interesting observations to generate much of the data currently available. Methods for assessing vitamin-E-like activity are based on making animals deficient in the vitamin and then restoring some aspect of function. These procedures are time-consuming, requiring a minimum of three weeks, and involve quantifying protection against deficiency signs.

Thin-film electronics in its myriad forms has underpinned much of the technological innovation in the fields of displays, sensors, and energy conversion over the past four decades. This technology also forms the basis of flexible electronics. Here we review the current status of flexible electronics and attempt to predict the future promise of these pervading technologies in healthcare, environmental monitoring, displays and human-machine interactivity, energy conversion, management and storage, and communication and wireless networks.