A Retrospective Pre-Post Treatment Study of Occupational Therapy Intervention for Children with Sensory Processing Challenges

Background: This study investigated the impact of an intensive, short-term program that incorporates the principles of sensory integration and relationship-based therapies with extensive parent collaboration. The goals were to identify measures sensitive to change and explore the relation between sensory modulation characteristics and change in behavior after intervention. Method: A retrospective chart review examined routine clinical data pre-post intervention from 179 children identified with sensory processing challenges without comorbid autism. Change in measures of adaptive behavior, emotional functioning, sensory-related behaviors, and motor functioning were evaluated. Relations between sensory modulation and behavior were explored. Results: Improvements were noted from pretreatment to postreatment on all measures of adaptive behavior, problem behaviors, sensory-related functions, and measures of motor function. Sensory craving symptoms were associated with a significant reduction in externalizing and behavior problems after intervention. Conclusion: This study provides preliminary support for the effectiveness of a novel treatment approach

Intersession Reliability and Within-Session Stability of a Novel Perception-Action Coupling Task

BACKGROUND: The perception-action coupling task (PACT) was designed as a more ecologically valid measure of alertness/reaction times compared to currently used measures by aerospace researchers. The purpose of this study was to assess the reliability, within-subject variability, and systematic bias associated with the PACT. METHODS: There were 16 subjects (men/women = 9/7; age = 27.8 +/- 3.6 yr) who completed 4 identical testing sessions. The PACT requires subjects to make judgements on whether a virtual ball could fit into an aperture. For each session, subjects completed nine cycles of the PACT, with each cycle lasting 5 min. Judgement accuracy and reaction time parameters were calculated for each cycle. Systematic bias was assessed with repeated-measures ANOVA, reliability with intraclass correlation coefficients (ICC), and within-subject variability with coefficients of variation (CVTE). RESULTS: Initiation time (Mean = 0.1065 s) showed the largest systematic bias, requiring the elimination of three cycles to reduce bias, with all other variables requiring, at the most, one. All variables showed acceptable reliability (ICC > 0.70) and within-subject variability (CVTE <20%) with only one cycle after elimination of the first three cycles. CONCLUSIONS: With a three-cycle familiarization period, the PACT was found to be reliable and stable

Playing with the future: social irrealism and the politics of aesthetics

In this paper we wish to explore the political possibilities of video games. Numerous scholars now take seriously the place of popular culture in the remaking of our geographies, but video games still lag behind. For us, this tendency reflects a general response to them as imaginary spaces that are separate from everyday life and 'real' politics. It is this disconnect between abstraction and lived experience that we complicate by defining play as an event of what Brian Massumi calls lived abstraction. We wish to short-circuit the barriers that prevent the aesthetic resonating with the political and argue that through their enactment, video games can animate fantastical futures that require the player to make, and reflect upon, profound ethical decisions that can be antagonistic to prevailing political imaginations. We refer to this as social irrealism to demonstrate that reality can be understood through the impossible and the imagined

THE B LYMPHOCYTE DIFFERENTIATION FACTOR (BAFF) IS EXPRESSED IN THE AIRWAYS OF CHILDREN WITH CF AND IN LUNGS OF MICE INFECTED WITH PSEUDOMONAS AERUGINOSA

Background Chronic lung infection with Pseudomonas aeruginosa remains a major cause of mortality and morbidity among individuals with CF. Expression of mediators promoting recruitment and differentiation of B cells, or supporting antibody production is poorly understood yet could be key to controlling infection. Methods BAFF was measured in BAL from children with CF, both with and without P. aeruginosa, and controls. Mice were intra-nasally infected with P. aeruginosa strain LESB65 for up to 7 days. Cellular infiltration and expression of B cell chemoattractants and B cell differentiation factor, BAFF were measured in lung tissue. Results BAFF expression was elevated in both P. aeruginosa negative and positive CF patients and in P. aeruginosa infected mice post infection. Expression of the B cell chemoattractants CXCL13, CCL19 and CCL21 increased progressively post infection. Conclusions In a mouse model, infection with P. aeruginosa was associated with elevated expression of BAFF and other B cell chemoattractants suggesting a role for airway B cell recruitment and differentiation in the local adaptive immune response to P. aeruginosa. The paediatric CF airway, irrespective of pseudomonal infection, was found to be associated with an elevated level of BAFF implying that BAFF expression is not specific to pseudomonas infection and may be a feature of the CF airway. Despite the observed presence of a potent B cell activator, chronic colonisation is common suggesting that this response is ineffective

Compositional Variations between Adult and Infant Skin Microbiome: An Update

Human skin and its commensal microbiome form the first layer of protection to the outside world. A dynamic microbial ecosystem of bacteria, fungi and viruses, with the potential to respond to external insult, the skin microbiome has been shown to evolve over the life course with an alteration in taxonomic composition responding to altered microenvironmental conditions on human skin. This work sought to investigate the taxonomic, diversity and functional differences between infant and adult leg skin microbiomes. A 16S rRNA gene-based metataxonomic analysis revealed significant differences between the infant and adult skin groups, highlighting differential microbiome profiles at both the genus and species level. Diversity analysis reveals differences in the overall community structure and associated differential predicted functional profiles between the infant and adult skin microbiome suggest differing metabolic processes are present between the groups. These data add to the available information on the dynamic nature of skin microbiome during the life course and highlight the predicted differential microbial metabolic process that exists on infant and adult skin, which may have an impact on the future design and use of cosmetic products that are produced to work in consort with the skin microbiome

The Curious Case of Arenavirus Entry, and Its Inhibition

Arenaviruses comprise a diverse family of enveloped negative-strand RNA viruses that are endemic to specific rodent hosts worldwide. Several arenaviruses cause severe hemorrhagic fevers in humans, including Junín and Machupo viruses in South America and Lassa fever virus in western Africa. Arenavirus entry into the host cell is mediated by the envelope glycoprotein complex, GPC. The virion is endocytosed on binding to a cell-surface receptor, and membrane fusion is initiated in response to physiological acidification of the endosome. As with other class I virus fusion proteins, GPC-mediated membrane fusion is promoted through a regulated sequence of conformational changes leading to formation of the classical postfusion trimer-of-hairpins structure. GPC is, however, unique among the class I fusion proteins in that the mature complex retains a stable signal peptide (SSP) as a third subunit, in addition to the canonical receptor-binding and fusion proteins. We will review the curious properties of the tripartite GPC complex and describe evidence that SSP interacts with the fusion subunit to modulate pH-induced activation of membrane fusion. This unusual solution to maintaining the metastable prefusion state of GPC on the virion and activating the class I fusion cascade at acidic pH provides novel targets for antiviral intervention

Exercise therapy, manual therapy, or both, for osteoarthritis of the hip or knee: a factorial randomised controlled trial protocol

<p>Abstract</p> <p>Background</p> <p>Non-pharmacological, non-surgical interventions are recommended as the first line of treatment for osteoarthritis (OA) of the hip and knee. There is evidence that exercise therapy is effective for reducing pain and improving function in patients with knee OA, some evidence that exercise therapy is effective for hip OA, and early indications that manual therapy may be efficacious for hip and knee OA. There is little evidence as to which approach is more effective, if benefits endure, or if providing these therapies is cost-effective for the management of this disorder. The MOA Trial (Management of OsteoArthritis) aims to test the effectiveness of two physiotherapy interventions for improving disability and pain in adults with hip or knee OA in New Zealand. Specifically, our primary objectives are to investigate whether:</p> <p>1. Exercise therapy versus no exercise therapy improves disability at 12 months;</p> <p>2. Manual physiotherapy versus no manual therapy improves disability at 12 months;</p> <p>3. Providing physiotherapy programmes in addition to usual care is more cost-effective than usual care alone in the management of osteoarthritis at 24 months.</p> <p>Methods</p> <p>This is a 2 × 2 factorial randomised controlled trial. We plan to recruit 224 participants with hip or knee OA. Eligible participants will be randomly allocated to receive either: (a) a supervised multi-modal exercise therapy programme; (b) an individualised manual therapy programme; (c) both exercise therapy and manual therapy; or, (d) no trial physiotherapy. All participants will continue to receive usual medical care. The outcome assessors, orthopaedic surgeons, general medical practitioners, and statistician will be blind to group allocation until the statistical analysis is completed. The trial is funded by Health Research Council of New Zealand Project Grants (Project numbers 07/199, 07/200).</p> <p>Discussion</p> <p>The MOA Trial will be the first to investigate the effectiveness and cost-effectiveness of providing physiotherapy programmes of this kind, for the management of pain and disability in adults with hip or knee OA.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry ref: ACTRN12608000130369.</p

Chemokine Binding Protein M3 of Murine Gammaherpesvirus 68 Modulates the Host Response to Infection in a Natural Host

Murine γ-herpesvirus 68 (MHV-68) infection of Mus musculus-derived strains of mice is an attractive model of γ-herpesvirus infection. Surprisingly, however, ablation of expression of MHV-68 M3, a secreted protein with broad chemokine-binding properties in vitro, has no discernable effect during experimental infection via the respiratory tract. Here we demonstrate that M3 indeed contributes significantly to MHV-68 infection, but only in the context of a natural host, the wood mouse (Apodemus sylvaticus). Specifically, M3 was essential for two features unique to the wood mouse: virus-dependent inducible bronchus-associated lymphoid tissue (iBALT) in the lung and highly organized secondary follicles in the spleen, both predominant sites of latency in these organs. Consequently, lack of M3 resulted in substantially reduced latency in the spleen and lung. In the absence of M3, splenic germinal centers appeared as previously described for MHV-68-infected laboratory strains of mice, further evidence that M3 is not fully functional in the established model host. Finally, analyses of M3's influence on chemokine and cytokine levels within the lungs of infected wood mice were consistent with the known chemokine-binding profile of M3, and revealed additional influences that provide further insight into its role in MHV-68 biology

Development and validation of a targeted gene sequencing panel for application to disparate cancers

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy