Formation of cortical plasticity in older adults following tDCS and motor training

Neurodegeneration accompanies the process of natural aging, reducing the ability to perform functional daily activities. Transcranial direct current stimulation (tDCS) alters neuronal excitability and motor performance; however its beneficial effect on the induction of primary motor cortex (M1) plasticity in older adults is unclear. Moreover, little is known as to whether the tDCS electrode arrangement differentially affects M1 plasticity and motor performance in this population. In a double-blinded, cross-over trial, we compared unilateral, bilateral and sham tDCS combined with visuomotor tracking, on M1 plasticity and motor performance of the non-dominant upper limb, immediately post and 30 min following stimulation. We found (a) unilateral and bilateral tDCS decreased tracking error by 12–22% at both time points; with sham decreasing tracking error by 10% at 30 min only, (b) at both time points, motor evoked potentials (MEPs) were facilitated (38–54%) and short-interval intracortical inhibition was released (21–36%) for unilateral and bilateral conditions relative to sham, (c) there were no differences between unilateral and bilateral conditions for any measure. These findings suggest that tDCS modulated elements of M1 plasticity, which improved motor performance irrespective of the electrode arrangement. The results provide preliminary evidence indicating that tDCS is a safe non-invasive tool to preserve or improve neurological function and motor control in older adults.

Modelling interplay in normative social systems: towards a heuristics formalism of agents and networks

The need for guiding model formulation of normative social systems in support of a digital ecosystem is introduced. Normative social systems improve the understanding of computational social processes in simulation and experimentation, and provide support for digital ecosystem developments. However, a successful simulation requires the appropriate implementation of a conceptual model. It is proposed that an heuristic formalism of agents, networks and environments, complements the conventional creative approach to model formulation by guiding the formulation of conceptual models via abstract components and facilitate interface with other components in a digital environment.

Fish oil diet associated with acute reperfusion related hemorrhage, and with reduced stroke-related sickness behaviors and motor impairment

Ischemic stroke is associated with motor impairment and increased incidence of affective disorders such as anxiety/clinical depression. In non-stroke populations, successful management of such disorders and symptoms has been reported following diet supplementation with long chain omega-3-polyunsaturated-fatty-acids (PUFAs). However, the potential protective effects of PUFA supplementation on affective behaviors after experimentally induced stroke and sham surgery have not been examined previously. This study investigated the behavioral effects of PUFA supplementation over a 6-week period following either middle cerebral artery occlusion or sham surgery in the hooded-Wistar rat. The PUFA diet supplied during the acclimation period prior to surgery was found to be associated with an increased risk of acute hemorrhage following the reperfusion component of the surgery. In surviving animals, PUFA supplementation did not influence infarct size as determined 6 weeks after surgery, but did decrease omega-6-fatty-acid levels, moderate sickness behaviors, acute motor impairment, and longer-term locomotor hyperactivity and depression/anxiety-like behavior.

Australia’s position on medicines policy in international forums: Intellectual property protection and public health

Universal access to affordable medicines, which are safe, efficacious and of high quality, and which are appropriately used, depends on national legislation that is in turn constrained by a range of international agreements. This regulatory configuration also affects the profitability of the pharmaceutical industry, domestic and international. Tensions and contradictions between industry profitability and public health objectives relate to access, innovation and regulation.

Changes in corticomotor excitability and inhibition after exercise are influenced by hand dominance and motor demand

Previous studies on handedness have often reported functional asymmetries in corticomotor excitability (CME) associated with voluntary movement. Recently, we have shown that the degree of post-exercise corticomotor depression (PED) and increase in short-interval cortical inhibition (SICI) after a repetitive finger movement task was less when the task was performed at a maximal voluntary rate (MVR) than when it was performed at a submaximal sustainable rate (SR). In the current study, we have compared the time course of PED and SICI in the dominant (DOM) and nondominant (NDOM) hands after an MVR and SR finger movement task to determine the influence of hand dominance and task demand. We tracked motor-evoked potential (MEP) amplitude from the first dorsal interosseous muscle of the DOM and NDOM hand for 20 min after a 10-s index finger flexion-extension task at MVR and SR. For all hand-task combinations, we report a period of PED and increased SICI lasting for up to 8 min. We find that the least demanding task, one that involved index finger movement of the DOM hand at SR, was associated with the greatest change in PED and SICI from baseline (63.6±5.7% and 79±2%, P<0.001, PED and SICI, respectively), whereas the most demanding task (MVR of the NDOM hand) was associated with the least change from baseline (PED: 88.1±3.6%, SICI: 103±2%; P<0.001). Our findings indicate that the changes in CME and inhibition associated with repetitive finger movement are influenced both by handedness and the degree of demand of the motor task and are inversely related to task demand, being smallest for an MVR task of the NDOM hand and greatest for an SR task of the DOM hand. The findings provide additional evidence for differences in neuronal processing between the dominant and nondominant hemispheres in motor control.

Nurse-led titration of angiotensin converting enzyme inhibitors, beta-adrenergic blocking agents, and angiotensin receptor blockers for people with heart failure with reduced ejection fraction

BACKGROUND: Heart failure is associated with high mortality and hospital readmissions. Beta-adrenergic blocking agents, angiotensin converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) can improve survival and reduce hospital readmissions and are recommended as first-line therapy in the treatment of heart failure. Evidence has also shown that there is a dose-dependent relationship of these medications with patient outcomes. Despite this evidence, primary care physicians are reluctant to up-titrate these medications. New strategies aimed at facilitating this up-titration are warranted. Nurse-led titration (NLT) is one such strategy. OBJECTIVES: To assess the effects of NLT of beta-adrenergic blocking agents, ACEIs, and ARBs in patients with heart failure with reduced ejection fraction (HFrEF) in terms of safety and patient outcomes. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials in the Cochrane Library (CENTRAL Issue 11 of 12, 19/12/2014), MEDLINE OVID (1946 to November week 3 2014), and EMBASE Classic and EMBASE OVID (1947 to 2014 week 50). We also searched reference lists of relevant primary studies, systematic reviews, clinical trial registries, and unpublished theses sources. We used no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing NLT of beta-adrenergic blocking agents, ACEIs, and/or ARBs comparing the optimisation of these medications by a nurse to optimisation by another health professional in patients with HFrEF. DATA COLLECTION AND ANALYSIS: Two review authors (AD & JC) independently assessed studies for eligibility and risk of bias. We contacted primary authors if we required additional information. We examined quality of evidence using the GRADE rating tool for RCTs. We analysed extracted data by risk ratio (RR) with 95% confidence interval (CI) for dichotomous data to measure effect sizes of intervention group compared with usual-care group. Meta-analyses used the fixed-effect Mantel-Haenszel method. We assessed heterogeneity between studies by Chi(2) and I(2). MAIN RESULTS: We included seven studies (1684 participants) in the review. One study enrolled participants from a residential care facility, and the other six studies from primary care and outpatient clinics. All-cause hospital admission data was available in four studies (556 participants). Participants in the NLT group experienced a lower rate of all-cause hospital admissions (RR 0.80, 95% CI 0.72 to 0.88, high-quality evidence) and fewer hospital admissions related to heart failure (RR 0.51, 95% CI 0.36 to 0.72, moderate-quality evidence) compared to the usual-care group. Six studies (902 participants) examined all-cause mortality. All-cause mortality was also lower in the NLT group (RR 0.66, 95% CI 0.48 to 0.92, moderate-quality evidence) compared to usual care. Approximately 27 deaths could be avoided for every 1000 people receiving NLT of beta-adrenergic blocking agents, ACEIs, and ARBs. Only three studies (370 participants) reported outcomes on all-cause and heart failure-related event-free survival. Participants in the NLT group were more likely to remain event free compared to participants in the usual-care group (RR 0.60, 95% CI 0.46 to 0.77, moderate-quality evidence). Five studies (966 participants) reported on the number of participants reaching target dose of beta-adrenergic blocking agents. This was also higher in the NLT group compared to usual care (RR 1.99, 95% CI 1.61 to 2.47, low-quality evidence). However, there was a substantial degree of heterogeneity in this pooled analysis. We rated the risk of bias in these studies as high mainly due to a lack of clarity regarding incomplete outcome data, lack of reporting on adverse events associated with the intervention, and the inability to blind participants and personnel. Participants in the NLT group reached maximal dose of beta-adrenergic blocking agents in half the time compared with participants in usual care. Two studies reported on adverse events; one of these studies stated there were no adverse events, and the other study found one adverse event but did not specify the type or severity of the adverse event. AUTHORS' CONCLUSIONS: Participants in the NLT group experienced fewer hospital admissions for any cause and an increase in survival and number of participants reaching target dose within a shorter time period. However, the quality of evidence regarding the proportion of participants reaching target dose was low and should be interpreted with caution. We found high-quality evidence supporting NLT as one strategy that may improve the optimisation of beta-adrenergic blocking agents resulting in a reduction in hospital admissions. Despite evidence of a dose-dependent relationship of beta-adrenergic blocking agents, ACEIs, and ARBs with improving outcomes in patients with HFrEF, the translation of this evidence into clinical practice is poor. NLT is one strategy that facilitates the implementation of this evidence into practice.

Access to knoledge in Brazil: new research on intellectual property, innovation and development

The present volume is the fruit of a research initiative on Access to Knowledge begun in 2004 by Yochai Benkler, Eddan Katz, and myself. Access to Knowledge is both a social movement and an approach to international and domestic policy. In the present era of globalization, intellectual property and information and communications technology are major determinants of wealth and power. The principle of access to knowledge argues that we best serve both human rights and economic development through policies that make knowledge, knowledge-creating tools, and nowledgeembedded goods as widely available as possible for decentralized innovation and use. Open technological standards, a balanced approach to intellectual property rights, and expansion of an open telecommunications infrastructure enable ordinary people around the world to benefit from the technological advances of the information age and allow them to generate a vibrant, participatory and democratic culture. Law plays a crucial role in securing access to knowledge, determining whether knowledge and knowledge goods are shared widely for the benefit of all, or controlled and monopolized for the benefit of a few.

On the optimality of the Friedman Rule with heterogeneous agents and non-linear income taxation

We study the optimal “inflation tax” in an environment with heterogeneous agents and non-linear income taxes. We first derive the general conditions needed for the optimality of the Friedman rule in this setup. These general conditions are distinct in nature and more easily interpretable than those obtained in the literature with a representative agent and linear taxation. We then study two standard monetary specifications and derive their implications for the optimality of the Friedman rule. For the shopping-time model the Friedman rule is optimal with essentially no restrictions on preferences or transaction technologies. For the cash-credit model the Friedman rule is optimal if preferences are separable between the consumption goods and leisure, or if leisure shifts consumption towards the credit good. We also study a generalized model which nests both models as special cases.