2,258 research outputs found
Uncertainty in climate change impacts on basin-scale freshwater resources ā preface to the special issue: the QUEST-GSI methodology and synthesis of results
This paper presents a preface to this Special Issue on the results of the QUEST-GSI (Global Scale Impacts) project on climate change impacts on catchment-scale water resources. A detailed description of the unified methodology, subsequently used in all studies in this issue, is provided. The project method involved running simulations of catchment-scale hydrology using a unified set of past and future climate scenarios, to enable a consistent analysis of the climate impacts around the globe. These scenarios include "policy-relevant" prescribed warming scenarios. This is followed by a synthesis of the key findings. Overall, the studies indicate that in most basins the models project substantial changes to river flow, beyond that observed in the historical record, but that in many cases there is considerable uncertainty in the magnitude and sign of the projected changes. The implications of this for adaptation activities are discussed
Statistical challenges in the development and evaluation of marker-based clinical tests
Exciting new technologies for assessing markers in human specimens are now available to evaluate unprecedented types and numbers of variations in DNA, RNA, proteins, or biological structures such as chromosomes. These markers, whether viewed individually, or collectively as a 'signature', have the potential to be useful for disease risk assessment, screening, early detection, prognosis, therapy selection, and monitoring for therapy effectiveness or disease recurrence. Successful translation from basic research findings to clinically useful test requires basic, translational, and regulatory sciences and a collaborative effort among individuals with varied types of expertise including laboratory scientists, technology developers, clinicians, statisticians, and bioinformaticians. The focus of this commentary is the many statistical challenges in translational marker research, specifically in the development and validation of marker-based tests that have clinical utility for therapeutic decision-making
A Peer-Based Approach to Reducing Stigma and Improving Mental Health Support for Medical Students
Abstract
Medical students experience a tremendous amount of stress during their training, which can have a profound effect on mental wellness. Several medical students at the University of Ottawa have created a peer-based program called Mind the Gap (MtG), which aims to improve mental health support and combat mental health-related stigma within the medical student community. The program consists of monthly meetings that invite students to discuss personal experiences and issues surrounding mental illness. The following article is a commentary outlining the MtG program, including its rationale and goals, and the challenges in implementing this type of program.Ā
RƩsumƩ
Les eĢtudiants en meĢdecine vivent un stress eĢnorme au cours de leur formation, ce qui peut avoir un impact profond sur leur bien-eĢtre mental. Plusieurs eĢtudiants en meĢdecine aĢ lāUniversiteĢ dāOttawa ont mis sur pied un programme appeleĢ Ā« Mind the Gap Ā» (MtG), qui vise aĢ ameĢliorer le soutien en santeĢ mentale et aĢ combattre la stigmatisation lieĢe aĢ la santeĢ mentale dans la communauteĢ meĢdicale eĢtudiante. Le programme est composeĢ de rencontres mensuelles qui permettent aux eĢtudiants de discuter de leurs expeĢriences personnelles et des probleĢmes lieĢs aĢ la maladie mentale. Lāarticle suivant est un commentaire donnant un apercĢ§u du programme MtG, incluant sa raison dāeĢtre et ses buts, et les deĢfis qui surviennent lors de la mise en place dāun tel programme.
Revisiting protein aggregation as pathogenic in sporadic Parkinson and Alzheimer diseases.
The gold standard for a definitive diagnosis of Parkinson disease (PD) is the pathologic finding of aggregated Ī±-synuclein into Lewy bodies and for Alzheimer disease (AD) aggregated amyloid into plaques and hyperphosphorylated tau into tangles. Implicit in this clinicopathologic-based nosology is the assumption that pathologic protein aggregation at autopsy reflects pathogenesis at disease onset. While these aggregates may in exceptional cases be on a causal pathway in humans (e.g., aggregated Ī±-synuclein in SNCA gene multiplication or aggregated Ī²-amyloid in APP mutations), their near universality at postmortem in sporadic PD and AD suggests they may alternatively represent common outcomes from upstream mechanisms or compensatory responses to cellular stress in order to delay cell death. These 3 conceptual frameworks of protein aggregation (pathogenic, epiphenomenon, protective) are difficult to resolve because of the inability to probe brain tissue in real time. Whereas animal models, in which neither PD nor AD occur in natural states, consistently support a pathogenic role of protein aggregation, indirect evidence from human studies does not. We hypothesize that (1) current biomarkers of protein aggregates may be relevant to common pathology but not to subgroup pathogenesis and (2) disease-modifying treatments targeting oligomers or fibrils might be futile or deleterious because these proteins are epiphenomena or protective in the human brain under molecular stress. Future precision medicine efforts for molecular targeting of neurodegenerative diseases may require analyses not anchored on current clinicopathologic criteria but instead on biological signals generated from large deeply phenotyped aging populations or from smaller but well-defined genetic-molecular cohorts
A cooperative instinct
Acting on a gut feeling may sometimes lead to poor decisions, but it will usually support the common good, according to a study showing that human intuition favours cooperative, rather than selfish, behaviour
Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and a commercial BPI3V vaccine in dairy calves
peer-reviewedBackground There is a need to improve vaccination against respiratory pathogens in calves by stimulation of local immunity at the site of pathogen entry at an early stage in life. Ideally such a vaccine preparation would not be inhibited by the maternally derived antibodies. Additionally, localized immune response at the site of infection is also crucial to control infection at the site of entry of virus. The present study investigated the response to an intranasal bovine parainfluenza 3 virus (BPI3V) antigen preparation encapsulated in PLGA (poly dl-lactic-co-glycolide) nanoparticles in the presence of pre-existing anti-BPI3V antibodies in young calves and comparing it to a commercially available BPI3V respiratory vaccine.
Results
There was a significant (Pā<ā0.05) increase in BPI3V-specific IgA in the nasal mucus of the BPI3V nanoparticle vaccine group alone. Following administration of the nanoparticle vaccine an early immune response was induced that continued to grow until the end of study and was not observed in the other treatment groups. Virus specific serum IgG response to both the nanoparticle vaccine and commercial live attenuated vaccine showed a significant (Pā<ā0.05) rise over the period of study. However, theĀ cell mediated immune response observed didnāt show any significant rise in any of the treatment groups.
Conclusion
Calves administered theĀ intranasal nanoparticle vaccine induced significantly greater mucosal IgA responses, compared to the other treatment groups. This suggests an enhanced, sustained mucosal-based immunological response to the BPI3V nanoparticle vaccine in the face of pre-existing antibodies to BPI3V, which are encouraging and potentially useful characteristics of a candidate vaccine. However, ability of nanoparticle vaccine in eliciting cell mediated immune response needs further investigation. More sustained local mucosal immunity induced by nanoparticle vaccine has obvious potential if it translates into enhanced protective immunity in the face of virus outbreak
Higher Derivative Corrections to R-charged Black Holes: Boundary Counterterms and the Mass-Charge Relation
We carry out the holographic renormalization of Einstein-Maxwell theory with
curvature-squared corrections. In particular, we demonstrate how to construct
the generalized Gibbons-Hawking surface term needed to ensure a perturbatively
well-defined variational principle. This treatment ensures the absence of ghost
degrees of freedom at the linearized perturbative order in the
higher-derivative corrections. We use the holographically renormalized action
to study the thermodynamics of R-charged black holes with higher derivatives
and to investigate their mass to charge ratio in the extremal limit. In five
dimensions, there seems to be a connection between the sign of the higher
derivative couplings required to satisfy the weak gravity conjecture and that
violating the shear viscosity to entropy bound. This is in turn related to
possible constraints on the central charges of the dual CFT, in particular to
the sign of c-a.Comment: 30 pages. v2: references added, some equations simplifie
Algorithmic Complexity for Short Binary Strings Applied to Psychology: A Primer
Since human randomness production has been studied and widely used to assess
executive functions (especially inhibition), many measures have been suggested
to assess the degree to which a sequence is random-like. However, each of them
focuses on one feature of randomness, leading authors to have to use multiple
measures. Here we describe and advocate for the use of the accepted universal
measure for randomness based on algorithmic complexity, by means of a novel
previously presented technique using the the definition of algorithmic
probability. A re-analysis of the classical Radio Zenith data in the light of
the proposed measure and methodology is provided as a study case of an
application.Comment: To appear in Behavior Research Method
Game theory of mind
This paper introduces a model of ātheory of mindā, namely, how we represent the intentions and goals of others to optimise our mutual interactions. We draw on ideas from optimum control and game theory to provide a āgame theory of mindā. First, we consider the representations of goals in terms of value functions that are prescribed by utility or rewards. Critically, the joint value functions and ensuing behaviour are optimised recursively, under the assumption that I represent your value function, your representation of mine, your representation of my representation of yours, and so on ad infinitum. However, if we assume that the degree of recursion is bounded, then players need to estimate the opponent's degree of recursion (i.e., sophistication) to respond optimally. This induces a problem of inferring the opponent's sophistication, given behavioural exchanges. We show it is possible to deduce whether players make inferences about each other and quantify their sophistication on the basis of choices in sequential games. This rests on comparing generative models of choices with, and without, inference. Model comparison is demonstrated using simulated and real data from a āstag-huntā. Finally, we note that exactly the same sophisticated behaviour can be achieved by optimising the utility function itself (through prosocial utility), producing unsophisticated but apparently altruistic agents. This may be relevant ethologically in hierarchal game theory and coevolution
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