Immunosenescence and lymphomagenesis

One of the most important determinants of aging-related changes is a complex biological process emerged recently and called \u201cimmunosenescence\u201d. Immunosenescence refers to the inability of an aging immune system to produce an appropriate and effective response to challenge. This immune dysregulation may manifest as increased susceptibility to infection, cancer, autoimmune disease, and vaccine failure. At present, the relationship between immunosenescence and lymphoma in elderly patients is not defined in a satisfactory way. This review presents a brief overview of the interplay between aging, cancer and lymphoma, and the key topic of immunosenescence is addressed in the context of two main lymphoma groups, namely Non Hodgkin Lymphoma (NHL) and Hodgkin Lymphoma (HL). Epstein Barr Virus (EBV) plays a central role in the onset of neoplastic lymphoproliferation associated with immunological changes in aging, although the pathophysiology varies vastly among different disease entities. The interaction between immune dysfunction, immunosenescence and Epstein Barr Virus (EBV) infection appears to differ between NHL and HL, as well as between NHL subtypes

Changing behaviour 'more or less'-do theories of behaviour inform strategies for implementation and de-implementation? A critical interpretive synthesis

BACKGROUND: Implementing evidence-based care requires healthcare practitioners to do less of some things (de-implementation) and more of others (implementation). Variations in effectiveness of behaviour change interventions may result from failure to consider a distinction between approaches by which behaviour increases and decreases in frequency. The distinction is not well represented in methods for designing interventions. This review aimed to identify whether there is a theoretical rationale to support this distinction. METHODS: Using Critical Interpretative Synthesis, this conceptual review included papers from a broad range of fields (biology, psychology, education, business) likely to report approaches for increasing or decreasing behaviour. Articles were identified from databases using search terms related to theory and behaviour change. Articles reporting changes in frequency of behaviour and explicit use of theory were included. Data extracted were direction of behaviour change, how theory was operationalised, and theory-based recommendations for behaviour change. Analyses of extracted data were conducted iteratively and involved inductive coding and critical exploration of ideas and purposive sampling of additional papers to explore theoretical concepts in greater detail. RESULTS: Critical analysis of 66 papers and their theoretical sources identified three key findings: (1) 9 of the 15 behavioural theories identified do not distinguish between implementation and de-implementation (5 theories were applied to only implementation or de-implementation, not both); (2) a common strategy for decreasing frequency was substituting one behaviour with another. No theoretical basis for this strategy was articulated, nor were methods proposed for selecting appropriate substitute behaviours; (3) Operant Learning Theory makes an explicit distinction between techniques for increasing and decreasing frequency. DISCUSSION: Behavioural theories provide little insight into the distinction between implementation and de-implementation. Operant Learning Theory identified different strategies for implementation and de-implementation, but these strategies may not be acceptable in health systems. Additionally, if behaviour substitution is an approach for de-implementation, further investigation may inform methods or rationale for selecting the substitute behaviour

Galaxy And Mass Assembly (GAMA): end of survey report and data release 2

The Galaxy And Mass Assembly (GAMA) survey is one of the largest contemporary spectroscopic surveys of low-redshift galaxies. Covering an area of ~286 deg^2 (split among five survey regions) down to a limiting magnitude of r < 19.8 mag, we have collected spectra and reliable redshifts for 238,000 objects using the AAOmega spectrograph on the Anglo-Australian Telescope. In addition, we have assembled imaging data from a number of independent surveys in order to generate photometry spanning the wavelength range 1 nm - 1 m. Here we report on the recently completed spectroscopic survey and present a series of diagnostics to assess its final state and the quality of the redshift data. We also describe a number of survey aspects and procedures, or updates thereof, including changes to the input catalogue, redshifting and re-redshifting, and the derivation of ultraviolet, optical and near-infrared photometry. Finally, we present the second public release of GAMA data. In this release we provide input catalogue and targeting information, spectra, redshifts, ultraviolet, optical and near-infrared photometry, single-component S\'ersic fits, stellar masses, H$\alpha$-derived star formation rates, environment information, and group properties for all galaxies with r < 19.0 mag in two of our survey regions, and for all galaxies with r < 19.4 mag in a third region (72,225 objects in total). The database serving these data is available at http://www.gama-survey.org/

Perceived Object Stability Depends on Multisensory Estimates of Gravity

BACKGROUND: How does the brain estimate object stability? Objects fall over when the gravity-projected centre-of-mass lies outside the point or area of support. To estimate an object's stability visually, the brain must integrate information across the shape and compare its orientation to gravity. When observers lie on their sides, gravity is perceived as tilted toward body orientation, consistent with a representation of gravity derived from multisensory information. We exploited this to test whether vestibular and kinesthetic information affect this visual task or whether the brain estimates object stability solely from visual information. METHODOLOGY/PRINCIPAL FINDINGS: In three body orientations, participants viewed images of objects close to a table edge. We measured the critical angle at which each object appeared equally likely to fall over or right itself. Perceived gravity was measured using the subjective visual vertical. The results show that the perceived critical angle was significantly biased in the same direction as the subjective visual vertical (i.e., towards the multisensory estimate of gravity). CONCLUSIONS/SIGNIFICANCE: Our results rule out a general explanation that the brain depends solely on visual heuristics and assumptions about object stability. Instead, they suggest that multisensory estimates of gravity govern the perceived stability of objects, resulting in objects appearing more stable than they are when the head is tilted in the same direction in which they fall

Feasibility, design and conduct of a pragmatic randomized controlled trial to reduce overweight and obesity in children: The electronic games to aid motivation to exercise (eGAME) study

<p>Abstract</p> <p>Background</p> <p>Childhood obesity has reached epidemic proportions in developed countries. Sedentary screen-based activities such as video gaming are thought to displace active behaviors and are independently associated with obesity. Active video games, where players physically interact with images onscreen, may have utility as a novel intervention to increase physical activity and improve body composition in children. The aim of the Electronic Games to Aid Motivation to Exercise (eGAME) study is to determine the effects of an active video game intervention over 6 months on: body mass index (BMI), percent body fat, waist circumference, cardio-respiratory fitness, and physical activity levels in overweight children.</p> <p>Methods/Design</p> <p>Three hundred and thirty participants aged 10–14 years will be randomized to receive either an active video game upgrade package or to a control group (no intervention).</p> <p>Discussion</p> <p>An overview of the eGAME study is presented, providing an example of a large, pragmatic randomized controlled trial in a community setting. Reflection is offered on key issues encountered during the course of the study. In particular, investigation into the feasibility of the proposed intervention, as well as robust testing of proposed study procedures is a critical step prior to implementation of a large-scale trial.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry ACTRN12607000632493</p

Rivastigmine Lowers Aβ and Increases sAPPα Levels, Which Parallel Elevated Synaptic Markers and Metabolic Activity in Degenerating Primary Rat Neurons

Overproduction of amyloid-β (Aβ) protein in the brain has been hypothesized as the primary toxic insult that, via numerous mechanisms, produces cognitive deficits in Alzheimer's disease (AD). Cholinesterase inhibition is a primary strategy for treatment of AD, and specific compounds of this class have previously been demonstrated to influence Aβ precursor protein (APP) processing and Aβ production. However, little information is available on the effects of rivastigmine, a dual acetylcholinesterase and butyrylcholinesterase inhibitor, on APP processing. As this drug is currently used to treat AD, characterization of its various activities is important to optimize its clinical utility. We have previously shown that rivastigmine can preserve or enhance neuronal and synaptic terminal markers in degenerating primary embryonic cerebrocortical cultures. Given previous reports on the effects of APP and Aβ on synapses, regulation of APP processing represents a plausible mechanism for the synaptic effects of rivastigmine. To test this hypothesis, we treated degenerating primary cultures with rivastigmine and measured secreted APP (sAPP) and Aβ. Rivastigmine treatment increased metabolic activity in these cultured cells, and elevated APP secretion. Analysis of the two major forms of APP secreted by these cultures, attributed to neurons or glia based on molecular weight showed that rivastigmine treatment significantly increased neuronal relative to glial secreted APP. Furthermore, rivastigmine treatment increased α-secretase cleaved sAPPα and decreased Aβ secretion, suggesting a therapeutic mechanism wherein rivastigmine alters the relative activities of the secretase pathways. Assessment of sAPP levels in rodent CSF following once daily rivastigmine administration for 21 days confirmed that elevated levels of APP in cell culture translated in vivo. Taken together, rivastigmine treatment enhances neuronal sAPP and shifts APP processing toward the α-secretase pathway in degenerating neuronal cultures, which mirrors the trend of synaptic proteins, and metabolic activity

Functional Analysis of the Kinome of the Wheat Scab Fungus Fusarium graminearum

As in other eukaryotes, protein kinases play major regulatory roles in filamentous fungi. Although the genomes of many plant pathogenic fungi have been sequenced, systematic characterization of their kinomes has not been reported. The wheat scab fungus Fusarium graminearum has 116 protein kinases (PK) genes. Although twenty of them appeared to be essential, we generated deletion mutants for the other 96 PK genes, including 12 orthologs of essential genes in yeast. All of the PK mutants were assayed for changes in 17 phenotypes, including growth, conidiation, pathogenesis, stress responses, and sexual reproduction. Overall, deletion of 64 PK genes resulted in at least one of the phenotypes examined, including three mutants blocked in conidiation and five mutants with increased tolerance to hyperosmotic stress. In total, 42 PK mutants were significantly reduced in virulence or non-pathogenic, including mutants deleted of key components of the cAMP signaling and three MAPK pathways. A number of these PK genes, including Fg03146 and Fg04770 that are unique to filamentous fungi, are dispensable for hyphal growth and likely encode novel fungal virulence factors. Ascospores play a critical role in the initiation of wheat scab. Twenty-six PK mutants were blocked in perithecia formation or aborted in ascosporogenesis. Additional 19 mutants were defective in ascospore release or morphology. Interestingly, F. graminearum contains two aurora kinase genes with distinct functions, which has not been reported in fungi. In addition, we used the interlog approach to predict the PK-PK and PK-protein interaction networks of F. graminearum. Several predicted interactions were verified with yeast two-hybrid or co-immunoprecipitation assays. To our knowledge, this is the first functional characterization of the kinome in plant pathogenic fungi. Protein kinase genes important for various aspects of growth, developmental, and infection processes in F. graminearum were identified in this study

Incorporating clinical guidelines through clinician decision-making

<p>Abstract</p> <p>Background</p> <p>It is generally acknowledged that a disparity between knowledge and its implementation is adversely affecting quality of care. An example commonly cited is the failure of clinicians to follow clinical guidelines. A guiding assumption of this view is that adherence should be gauged by a standard of conformance. At least some guideline developers dispute this assumption and claim that their efforts are intended to inform and assist clinical practice, not to function as standards of performance. However, their ability to assist and inform will remain limited until an alternative to the conformance criterion is proposed that gauges how evidence-based guidelines are incorporated into clinical decisions.</p> <p>Methods</p> <p>The proposed investigation has two specific aims to identify the processes that affect decisions about incorporating clinical guidelines, and then to develop ad test a strategy that promotes the utilization of evidence-based practices. This paper focuses on the first aim. It presents the rationale, introduces the clinical paradigm of treatment-resistant schizophrenia, and discusses an exemplar of clinician non-conformance to a clinical guideline. A modification of the original study is proposed that targets psychiatric trainees and draws on a cognitively rich theory of decision-making to formulate hypotheses about how the guideline is incorporated into treatment decisions. Twenty volunteer subjects recruited from an accredited psychiatry training program will respond to sixty-four vignettes that represent a fully crossed 2 × 2 × 2 × 4 within-subjects design. The variables consist of criteria contained in the clinical guideline and other relevant factors. Subjects will also respond to a subset of eight vignettes that assesses their overall impression of the guideline. Generalization estimating equation models will be used to test the study's principal hypothesis and perform secondary analyses.</p> <p>Implications</p> <p>The original design of phase two of the proposed investigation will be changed in recognition of newly published literature on the relative effectiveness of treatments for schizophrenia. It is suggested that this literature supports the notion that guidelines serve a valuable function as decision tools, and substantiates the importance of decision-making as the means by which general principles are incorporated into clinical practice.</p

Raman spectroscopy as a versatile tool for studying the properties of graphene.

Raman spectroscopy is an integral part of graphene research. It is used to determine the number and orientation of layers, the quality and types of edge, and the effects of perturbations, such as electric and magnetic fields, strain, doping, disorder and functional groups. This, in turn, provides insight into all sp(2)-bonded carbon allotropes, because graphene is their fundamental building block. Here we review the state of the art, future directions and open questions in Raman spectroscopy of graphene. We describe essential physical processes whose importance has only recently been recognized, such as the various types of resonance at play, and the role of quantum interference. We update all basic concepts and notations, and propose a terminology that is able to describe any result in literature. We finally highlight the potential of Raman spectroscopy for layered materials other than graphene