626 research outputs found

    Perforin-mediated cytotoxicity is critical for surveillance of spontaneous lymphoma

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    Immune surveillance by cytotoxic lymphocytes against cancer has been postulated for decades, but direct evidence for the role of cytotoxic lymphocytes in protecting against spontaneous malignancy has been lacking. As the rejection of many experimental cancers by cytotoxic T lymphocytes and natural killer cells is dependent on the pore-forming protein perforin (pfp), we examined pfp-deficient mice for increased cancer susceptibility. Here we show that pfp-deficient mice have a high incidence of malignancy in distinct lymphoid cell lineages (T, B, NKT), indicating a specific requirement for pfp in protection against lymphomagenesis. The susceptibility to lymphoma was accentuated by simultaneous lack of expression of the p53 gene, mutations in which also commonly predispose to human malignancies, including lymphoma. In contrast, the incidence and age of onset of sarcoma was unaffected in p53-deficient mice. Pfp-deficient mice were at least 1,000-fold more susceptible to these lymphomas when transplanted, compared with immunocompetent mice in which tumor rejection was controlled by CD8(+) T lymphocytes. This study is the first that implicates direct cytotoxicity by lymphocytes in regulating lymphomagenesis

    CJCheck Stage 1: development and testing of a checklist for reporting community juries – Delphi process and analysis of studies published in 1996–2015

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    Background Opportunities for community members to actively participate in policy development are increasing. Community/citizen's juries (CJs) are a deliberative democratic process aimed to illicit informed community perspectives on difficult topics. But how comprehensive these processes are reported in peer-reviewed literature is unknown. Adequate reporting of methodology enables others to judge process quality, compare outcomes, facilitate critical reflection and potentially repeat a process. We aimed to identify important elements for reporting CJs, to develop an initial checklist and to review published health and health policy CJs to examine reporting standards. Design Using the literature and expertise from CJ researchers and policy advisors, a list of important CJ reporting items was suggested and further refined. We then reviewed published CJs within the health literature and used the checklist to assess the comprehensiveness of reporting. Results CJCheck was developed and examined reporting of CJ planning, juror information, procedures and scheduling. We screened 1711 studies and extracted data from 38. No studies fully reported the checklist items. The item most consistently reported was juror numbers (92%, 35/38), while least reported was the availability of expert presentations (5%, 2/38). Recruitment strategies were described in 66% of studies (25/38); however, the frequency and timing of deliberations was inadequately described (29%, 11/38). Conclusions Currently CJ publications in health and health policy literature are inadequately reported, hampering their use in policy making. We propose broadening the CJCheck by creating a reporting standards template in collaboration with international CJ researchers, policy advisors and consumer representatives to ensure standardized, systematic and transparent reporting.RT was supported by a NHMRC Screening and Test Evaluation Program (STEP) Grant (#633033). RS was supported by a Bond University Vice Chancellor’s Research Grant Scheme. CD, SMC and LR received funding support from NHMRC Project Grant (#1023197). CD received funding support from a NHMRC Project Grant (#1083079). SMC is funded through NHMRC Career Development Fellowship (#1032963). JMS was funded by an Australian National Preventive Health Agency Fellowship (20STR2013F) and an NHMRC Capacity Building Grant (565501)

    The politics of the teaching of reading

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    Historically, political debates have broken out over how to teach reading in primary schools and infant classrooms. These debates and “reading wars” have often resulted from public concerns and media reportage of a fall in reading standards. They also reflect the importance placed on learning to read by parents, teachers, employers, and politicians. Public and media-driven controversies over the teaching of reading have resulted in intense public and professional debates over which specific methods and materials to use with beginning readers and with children who have reading difficulties. Recently, such debates have led to a renewed emphasis on reading proficiency and “standardized” approaches to teaching reading and engaging with literacy. The universal acceptance of the importance of learning to read has also led to vested interests in specific methods, reading programmes, and early literacy assessments amongst professional, business, commercial, and parental lobbying groups. This article traces these debates and the resulting growing support for a quantitative reductionist approach to early-reading programmes

    The Holocene isotopic record of aquatic cellulose from Lake Äntu Sinijärv, Estonia: Influence of changing climate and organic-matter sources

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    The well characterized oxygen-isotopic fractionation during cellulose biosynthesis has been utilised by numerous studies of stable isotopes in fine-grained aquatic cellulose. We measured the δ13Ccelluloseand δ18Ocellulosevalues of bulk cellulose and moss fragments from an ∼11.4ka-long core obtained from a shallow, productive, spring-fed, hardwater lake, Äntu Sinijärv, Estonia (59˚3.8′N; 26˚14.5′E; 94.6 m a.s.l.; maximum depth 7.3 m), in order to reconstruct regional Holocene climate and lake-basin evolution. Isotopically, the modern waterbody is a well-behaved, open, hydrological system with negligible evaporative effects. Cellulose-isotope records were compared with down-core measurements of loss-on-ignition (LOI), carbonate and mineral contents, total organic carbon (TOC), total nitrogen (TN), C/N ratio, δ13CTOC, biomarker indices (Palgand Paq), published palaeoecological data and a δ18Ocarbonaterecord from the same palaeolake. Green microalgae, freshwater macroalgae (Chara) and aquatic bryophytes were important sources of sedimentary cellulose during different phases in the environmental history of the lake. Although a strong palaeoclimatic imprint can be detected in the δ18Ocelluloserecord from Äntu Sinijärv, notably the Preboreal oscillation, the 8.2ka event and an unnamed cold oscillation ∼3.25ka BP, the isotopic signal of these events may have been amplified by increases in18O-depleted spring snowmelt. In contrast, δ13Ccellulosewas tightly coupled to the Holocene evolution of terrestrial ecosystems and soils by significant inputs of biogenic carbon from the catchment and sublacustrine springs. During the early Holocene, ∼11 – 9ka BP, the δ18Ocelluloseand δ18Ocarbonaterecords diverge markedly, which can be attributed to “no-analogue” seasonal, climatic, hydrological and isotopic conditions resulting from orbital forcing and residual ice-sheet impacts

    Influence of an alkalizing supplement on markers of endurance performance using a double-blind placebo-controlled design

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    <p>Abstract</p> <p>Background</p> <p>Previous research has shown that ingestion of substances that enhance the body's hydrogen ion buffering capacity during high intensity exercise can improve exercise performance. The present study aimed to determine whether the chronic ingestion of an alkalizing supplement, which purports to enhance both intracellular and extracellular buffering capacity, could impact cardiorespiratory and performance markers in trained Nordic skiers.</p> <p>Methods</p> <p>Twenty-four skiers (12 men, 12 women), matched for upper body power (UBP), were split into treatment and placebo groups. The treatment group ingested Alka-Myte<sup>®</sup>-based alkalizing tablets (1 tablet/22.7 kg body mass/day) over seven successive days while the placebo group consumed placebo tablets (i.e., no Alka-Myte<sup>®</sup>) at the same dosage. Prior to tablet ingestion (i.e., pre-testing), both groups completed a constant power UBP test, three successive 10-sec UBP tests, and then a 60-sec UBP test. Next, skiers completed the 7-day ingestion of their assigned tablets followed immediately by a repeat of the same UBP tests (i.e., post-testing). Neither the skiers nor the researchers were aware of which tablets were being consumed by either group until after all testing was complete. Dependent measures for analysis included heart rate (HR), oxygen consumption (VO<sub>2</sub>), minute ventilation (V<sub>E</sub>), blood lactate (LA), as well as 10-sec (W10, W) and 60-sec (W60, W) UBP. All data were evaluated using a two-factor multivariate repeated measures ANOVA with planned contrasts for post-hoc testing (alpha = 0.05).</p> <p>Results</p> <p>Post-testing cardiorespiratory (HR, VO<sub>2</sub>, V<sub>E</sub>) and LA measures for the treatment group tended to be significantly lower when measured for both constant power and UBP60 tests, while measures of both 10-sec (W10: 229 to 243 W) and 60-sec UBP (W60: 190 to 198 W) were significantly higher (<it>P </it>< 0.05). In contrast, there were no significant changes for the placebo group (P > 0.05).</p> <p>Conclusions</p> <p>Following the 7-day loading phase of Alka-Myte<sup>®</sup>-based alkalizing tablets, trained Nordic skiers experienced significantly lower cardiorespiratory stress, lower blood lactate responses, and higher UBP measures. Thus, the use of this supplement appeared to impart an ergogenic benefit to the skiers that may be similar to the effects expected from consuming well-studied extracellular buffering agents such as sodium bicarbonate.</p

    Rescaling quality of life values from discrete choice experiments for use as QALYs: a cautionary tale

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    Background: Researchers are increasingly investigating the potential for ordinal tasks such as ranking and discrete choice experiments to estimate QALY health state values. However, the assumptions of random utility theory, which underpin the statistical models used to provide these estimates, have received insufficient attention. In particular, the assumptions made about the decisions between living states and the death state are not satisfied, at least for some people. Estimated values are likely to be incorrectly anchored with respect to death (zero) in such circumstances. Methods: Data from the Investigating Choice Experiments for the preferences of older people CAPability instrument (ICECAP) valuation exercise were analysed. The values (previously anchored to the worst possible state) were rescaled using an ordinal model proposed previously to estimate QALY-like values. Bootstrapping was conducted to vary artificially the proportion of people who conformed to the conventional random utility model underpinning the analyses. Results: Only 26% of respondents conformed unequivocally to the assumptions of conventional random utility theory. At least 14% of respondents unequivocally violated the assumptions. Varying the relative proportions of conforming respondents in sensitivity analyses led to large changes in the estimated QALY values, particularly for lower-valued states. As a result these values could be either positive (considered to be better than death) or negative (considered to be worse than death). Conclusion: Use of a statistical model such as conditional (multinomial) regression to anchor quality of life values from ordinal data to death is inappropriate in the presence of respondents who do not conform to the assumptions of conventional random utility theory. This is clearest when estimating values for that group of respondents observed in valuation samples who refuse to consider any living state to be worse than death: in such circumstances the model cannot be estimated. Only a valuation task requiring respondents to make choices in which both length and quality of life vary can produce estimates that properly reflect the preferences of all respondents

    Telepresence and the Role of the Senses

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    The telepresence experience can be evoked in a number of ways. A well-known example is a player of videogames who reports about a telepresence experience, a subjective experience of being in one place or environment, even when physically situated in another place. In this paper we set the phenomenon of telepresence into a theoretical framework. As people react subjectively to stimuli from telepresence, empirical studies can give more evidence about the phenomenon. Thus, our contribution is to bridge the theoretical with the empirical. We discuss theories of perception with an emphasis on Heidegger, Merleau-Ponty and Gibson, the role of the senses and the Spinozian belief procedure. The aim is to contribute to our understanding of this phenomenon. A telepresence-study that included the affordance concept is used to empirically study how players report sense-reactions to virtual sightseeing in two cities. We investigate and explore the interplay of the philosophical and the empirical. The findings indicate that it is not only the visual sense that plays a role in this experience, but all senses

    Predicted Relative Metabolomic Turnover (PRMT): determining metabolic turnover from a coastal marine metagenomic dataset

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    We present an approach in which the semantics of an XML language is defined by means of a transformation from an XML document model (an XML schema) to an application specific model. The application specific model implements the intended behavior of documents written in the language. A transformation is specified in a model transformation language used in the Model Driven Architecture (MDA) approach for software development. Our approach provides a better separation of three concerns found in XML applications: syntax, syntax processing logic and intended meaning of the syntax. It frees the developer of low-level syntactical details and improves the adaptability and reusability of XML applications. Declarative transformation rules and the explicit application model provide a finer control over the application parts affected by adaptations. Transformation rules and the application model for an XML language may be composed with the corresponding rules and application models defined for other XML languages. In that way we achieve reuse and composition of XML applications
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