Technological Change and Copyright Tariffs after CBC v. SODRAC (SCC 2015). Part 1

TECHNOLOGICAL NEUTRALITY “Technological neutrality” has emerged in recent Supreme Court jurisprudence as a guiding principle in the application of traditional copyright law to new digital contexts. The principle has been defined in a variety of competing ways, with disagreement about its meaning and effect being the central point of departure between the majority and minority rulings in the SODRAC case. How will the SODRAC case change or inform the application of technological neutrality in copyright law, both in respect of defining rights and their limits, and in the valuation of licenses at the Copyright Board? How might the decision impact other areas of law or policy beyond copyright

Targeting endogenous proteins for degradation through the affinity-directed protein missile system

Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible for many genes. Similarly, RNA interference approaches necessitate prolonged treatments, can lead to incomplete knockdowns and are often associated with off-target effects. Targeted proteolysis can overcome these limitations. In this report, we describe an affinity-directed protein missile (AdPROM) system that harbours the von Hippel–Lindau (VHL) protein, the substrate receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders that selectively bind and recruit endogenous target proteins to the CUL2-E3 ligase complex for ubiquitination and proteasomal degradation. By using synthetic monobodies that selectively bind the protein tyrosine phosphatase SHP2 and a camelid-derived VHH nanobody that selectively binds the human ASC protein, we demonstrate highly efficient AdPROM-mediated degradation of endogenous SHP2 and ASC in human cell lines. We show that AdPROM-mediated loss of SHP2 in cells impacts SHP2 biology. This study demonstrates for the first time that small polypeptide binders that selectively recognize endogenous target proteins can be exploited for AdPROM-mediated destruction of the target proteins.</jats:p

In-Space Assembly Capability Assessment for Potential Human Exploration and Science Applications

Human missions to Mars present several major challenges that must be overcome, including delivering multiple large mass and volume elements, keeping the crew safe and productive, meeting cost constraints, and ensuring a sustainable campaign. Traditional methods for executing human Mars missions minimize or eliminate in-space assembly, which provides a narrow range of options for addressing these challenges and limits the types of missions that can be performed. This paper discusses recent work to evaluate how the inclusion of in-space assembly in space mission architectural concepts could provide novel solutions to address these challenges by increasing operational flexibility, robustness, risk reduction, crew health and safety, and sustainability. A hierarchical framework is presented to characterize assembly strategies, assembly tasks, and the required capabilities to assemble mission systems in space. The framework is used to identify general mission system design considerations and assembly system characteristics by assembly strategy. These general approaches are then applied to identify potential in-space assembly applications to address each challenge. Through this process, several focus areas were identified where applications of in-space assembly could affect multiple challenges. Each focus area was developed to identify functions, potential assembly solutions and operations, key architectural trades, and potential considerations and implications of implementation. This paper helps to identify key areas to investigate were potentially significant gains in addressing the challenges with human missions to Mars may be realized, and creates a foundation on which to further develop and analyze in-space assembly concepts and assembly-based architectures

Core competencies in the science and practice of knowledge translation: description of a Canadian strategic training initiative

<p>Abstract</p> <p>Background</p> <p>Globally, healthcare systems are attempting to optimize quality of care. This challenge has resulted in the development of implementation science or knowledge translation (KT) and the resulting need to build capacity in both the science and practice of KT.</p> <p>Findings</p> <p>We are attempting to meet these challenges through the creation of a national training initiative in KT. We have identified core competencies in this field and have developed a series of educational courses and materials for three training streams. We report the outline for this approach and the progress to date.</p> <p>Conclusions</p> <p>We have prepared a strategy to develop, implement, and evaluate a national training initiative to build capacity in the science and practice of KT. Ultimately through this initiative, we hope to meet the capacity demand for KT researchers and practitioners in Canada that will lead to improved care and a strengthened healthcare system.</p

A neurocomputational account of how inflammation enhances sensitivity to punishments versus rewards

BACKGROUND: Inflammation rapidly impairs mood and cognition and, when severe, can appear indistinguishable from major depression. These sickness responses are characterized by an acute reorientation of motivational state; pleasurable activities are avoided, and sensitivity to negative stimuli is enhanced. However, it remains unclear how these rapid shifts in behavior are mediated within the brain. METHODS: Here, we combined computational modeling of choice behavior, experimentally induced inflammation, and functional brain imaging (functional magnetic resonance imaging) to describe these mechanisms. Using a double-blind, randomized crossover study design, 24 healthy volunteers completed a probabilistic instrumental learning task on two separate occasions, one 3 hours after typhoid vaccination and one 3 hours after saline (placebo) injection. Participants learned to select high probability reward (win £1) and avoid high probability punishment (lose £1) stimuli. An action-value learning algorithm was fit to the observed behavior, then used within functional magnetic resonance imaging analyses to identify neural coding of prediction error signals driving motivational learning. RESULTS: Inflammation acutely biased behavior, enhancing punishment compared with reward sensitivity, through distinct actions on neural representations of reward and punishment prediction errors within the ventral striatum and anterior insula. Consequently, choice options leading to potential rewards were less behaviorally attractive, and those leading to punishments were more aversive. CONCLUSIONS: Our findings demonstrate the neural mediation of a rapid, state-dependent reorientation of reward versus punishment sensitivity during inflammation. This mechanism may aid the adaptive reallocation of metabolic resources during acute sickness but might also account for

The systematic guideline review: method, rationale, and test on chronic heart failure

Background: Evidence-based guidelines have the potential to improve healthcare. However, their de-novo-development requires substantial resources-especially for complex conditions, and adaptation may be biased by contextually influenced recommendations in source guidelines. In this paper we describe a new approach to guideline development-the systematic guideline review method (SGR), and its application in the development of an evidence-based guideline for family physicians on chronic heart failure (CHF). Methods: A systematic search for guidelines was carried out. Evidence-based guidelines on CHF management in adults in ambulatory care published in English or German between the years 2000 and 2004 were included. Guidelines on acute or right heart failure were excluded. Eligibility was assessed by two reviewers, methodological quality of selected guidelines was appraised using the AGREE instrument, and a framework of relevant clinical questions for diagnostics and treatment was derived. Data were extracted into evidence tables, systematically compared by means of a consistency analysis and synthesized in a preliminary draft. Most relevant primary sources were re-assessed to verify the cited evidence. Evidence and recommendations were summarized in a draft guideline. Results: Of 16 included guidelines five were of good quality. A total of 35 recommendations were systematically compared: 25/35 were consistent, 9/35 inconsistent, and 1/35 un-rateable (derived from a single guideline). Of the 25 consistencies, 14 were based on consensus, seven on evidence and four differed in grading. Major inconsistencies were found in 3/9 of the inconsistent recommendations. We re-evaluated the evidence for 17 recommendations (evidence-based, differing evidence levels and minor inconsistencies) - the majority was congruent. Incongruity was found where the stated evidence could not be verified in the cited primary sources, or where the evaluation in the source guidelines focused on treatment benefits and underestimated the risks. The draft guideline was completed in 8.5 man-months. The main limitation to this study was the lack of a second reviewer. Conclusion: The systematic guideline review including framework development, consistency analysis and validation is an effective, valid, and resource saving-approach to the development of evidence-based guidelines

Willingness of Men Who Have Sex with Men (MSM) in the United States to Be Circumcised as Adults to Reduce the Risk of HIV Infection

BACKGROUND: Circumcision reduces HIV acquisition among heterosexual men in Africa, but it is unclear if circumcision may reduce HIV acquisition among men who have sex with men (MSM) in the United States, or whether MSM would be willing to be circumcised if recommended. METHODS: We interviewed presumed-HIV negative MSM at gay pride events in 2006. We asked uncircumcised respondents about willingness to be circumcised if it were proven to reduce risk of HIV among MSM and perceived barriers to circumcision. Multivariate logistic regression was used to identify covariates associated with willingness to be circumcised. RESULTS: Of 780 MSM, 133 (17%) were uncircumcised. Of these, 71 (53%) were willing to be circumcised. Willingness was associated with black race (exact odds ratio [OR]: 3.4, 95% confidence interval [CI]: 1.3-9.8), non-injection drug use (OR: 6.1, 95% CI: 1.8-23.7) and perceived reduced risk of penile cancer (OR: 4.7, 95% CI: 2.0-11.9). The most commonly endorsed concerns about circumcision were post-surgical pain and wound infection. CONCLUSIONS: Over half of uncircumcised MSM, especially black MSM, expressed willingness to be circumcised. Perceived risks and benefits of circumcision should be a part of educational materials if circumcision is recommended for MSM in the United States

Five-year workplace wellness intervention in the NHS

aims: Poor health and well-being has been observed among NHS staff and has become a key focus in current public health policy. The objective of this study was to deliver and evaluate a five-year employee wellness programme aimed at improving the health and well-being of employees in a large NHS workplace. method: A theory-driven multi-level ecological workplace wellness intervention was delivered including health campaigns, provision of facilities and health-promotion activities to encourage employees to make healthy lifestyle choices and sustained behaviour changes. An employee questionnaire survey was distributed at baseline (n= 1,452) and at five years (n= 1,134), including measures of physical activity, BMI, diet, self-efficacy, social support, perceived gen-eral health and mood, smoking behaviours, self-reported sickness absence, perceived work performance and job satisfaction. results: Samples were comparable at baseline and follow-up. At five years, significantly more respondents actively travelled (by walking or cycling both to work and for non-work trips) and more were active while at work. Significantly more respondents met current recommendations for physical activity at five years than at baseline. Fewer employers reported ‘lack of time’ as a barrier to being physically active following the intervention. Significantly lower sickness absence, greater job satisfaction and greater organisational commitment was reported at five years than at baseline. conclusions: Improvements in health behaviours, reductions in sickness absence and improvements in job satisfaction and organisational commitment were observed following five years of a workplace wellness intervention for NHS employees. These findings suggest that health-promoting programmes should be embedded within NHS infrastructure

Humans and Insects Decide in Similar Ways

Behavioral ecologists assume that animals use a motivational mechanism for decisions such as action selection and time allocation, allowing the maximization of their fitness. They consider both the proximate and ultimate causes of behavior in order to understand this type of decision-making in animals. Experimental psychologists and neuroeconomists also study how agents make decisions but they consider the proximate causes of the behavior. In the case of patch-leaving, motivation-based decision-making remains simple speculation. In contrast to other animals, human beings can assess and evaluate their own motivation by an introspection process. It is then possible to study the declared motivation of humans during decision-making and discuss the mechanism used as well as its evolutionary significance. In this study, we combine both the proximate and ultimate causes of behavior for a better understanding of the human decision-making process. We show for the first time ever that human subjects use a motivational mechanism similar to small insects such as parasitoids [1] and bumblebees [2] to decide when to leave a patch. This result is relevant for behavioral ecologists as it supports the biological realism of this mechanism. Humans seem to use a motivational mechanism of decision making known to be adaptive to a heterogeneously distributed resource. As hypothesized by Hutchinson et al. [3] and Wilke and Todd [4], our results are consistent with the evolutionary shaping of decision making because hominoids were hunters and gatherers on food patches for more than two million years. We discuss the plausibility of a neural basis for the motivation mechanism highlighted here, bridging the gap between behavioral ecology and neuroeconomy. Thus, both the motivational mechanism observed here and the neuroeconomy findings are most likely adaptations that were selected for during ancestral times

Physiological and Psychological Effects of Deception on Pacing Strategy and Performance: A Review

The aim of an optimal pacing strategy during exercise is to enhance performance whilst ensuring physiological limits are not surpassed, which has been shown to result in a metabolic reserve at the end of the exercise. There has been debate surrounding the theoretical models that have been proposed to explain how pace is regulated, with more recent research investigating a central control of exercise regulation. Deception has recently emerged as a common, practical approach to manipulate key variables during exercise. There are a number of ways in which deception interventions have been designed, each intending to gain particular insights into pacing behaviour and performance. Deception methodologies can be conceptualised according to a number of dimensions such as deception timing (prior to or during exercise), presentation frequency (blind, discontinuous or continuous) and type of deception (performance, biofeedback or environmental feedback). However, research evidence on the effects of deception has been perplexing and the use of complex designs and varied methodologies makes it difficult to draw any definitive conclusions about how pacing strategy and performance are affected by deception. This review examines existing research in the area of deception and pacing strategies, and provides a critical appraisal of the different methodological approaches used to date. It is hoped that this analysis will inform the direction and methodology of future investigations in this area by addressing the mechanisms through which deception impacts upon performance and by elucidating the potential application of deception techniques in training and competitive settings