Harnessing the Therapeutic Potential of Th17 Cells

Th17 cells provide protective immunity to infections by fungi and extracellular bacteria as well as cancer but are also involved in chronic inflammation. The cells were first identified by their ability to produce interleukin 17A (IL-17A) and, subsequently, associated with chronic inflammation and autoimmunity. Th17 cells have some gene profile similarity with stem cells and can remain dormant in mucosal tissues for long periods. Indeed, recent studies suggest that functionally distinct subsets of pro- and anti-inflammatory Th17 cells can interchange phenotype and functions. For development, Th17 cells require activation of the transcription factors STAT3 and RORγt while RUNX1, c-Maf, and Aiolos are involved in changes of phenotype/functions. Attempts to harness Th17 cells against pathogens and cancer using vaccination strategies are being explored. The cells gain protective abilities when induced to produce interferon γ (IFNγ). In addition, treatment with antibodies to IL-17 is effective in treating patients with psoriasis, psoriatic arthritis, and refectory rheumatoid arthritis. Moreover, since RORγt is a nuclear receptor, it is likely to be a potential future drug target for modulating Th17 functions. This review explores pathways through which Th17 subsets are induced, the molecular basis of their plasticity, and potential therapeutic strategies for their modulation in diseases

Grasping the changes seen in older adults when reaching for objects of varied texture.

Old age is associated with reduced mobility of the hand. To investigate age related decline when reaching-to-lift an object we used sophisticated kinematic apparatus to record reaches carried out by healthy older and younger participants. Three objects of different widths were placed at three different distances, with objects having either a high or low friction surface (i.e. rough or slippery). Older participants showed quantitative differences to their younger counterparts - movements were slower and peak speed did not scale with object distance. There were also qualitative differences with older adults showing a greater propensity to stop the hand and adjust finger position before lifting objects. The older participants particularly struggled to lift wide slippery objects, apparently due to an inability to manipulate their grasp to provide the level of precision necessary to functionally enclose the object. These data shed light on the nature of age related changes in reaching-to-grasp movements and establish a powerful technique for exploring how different product designs will impact on prehensile behavior

Simulated Warming Differentially Affects the Growth and Competitive Ability of Centaurea maculosa Populations from Home and Introduced Ranges

Climate warming may drive invasions by exotic plants, thereby raising concerns over the risks of invasive plants. However, little is known about how climate warming influences the growth and competitive ability of exotic plants from their home and introduced ranges. We conducted a common garden experiment with an invasive plant Centaurea maculosa and a native plant Poa pratensis, in which a mixture of sand and vermiculite was used as a neutral medium, and contrasted the total biomass, competitive effects, and competitive responses of C. maculosa populations from Europe (home range) and North America (introduced range) under two different temperatures. The warming-induced inhibitory effects on the growth of C. maculosa alone were stronger in Europe than in North America. The competitive ability of C. maculosa plants from North America was greater than that of plants from Europe under the ambient condition whereas this competitive ability followed the opposite direction under the warming condition, suggesting that warming may enable European C. maculosa to be more invasive. Across two continents, warming treatment increased the competitive advantage instead of the growth advantage of C. maculosa, suggesting that climate warming may facilitate C. maculosa invasions through altering competitive outcomes between C. maculosa and its neighbors. Additionally, the growth response of C. maculosa to warming could predict its ability to avoid being suppressed by its neighbors

Voice disorders and mental health in teachers: a cross-sectional nationwide study

International audienceBACKGROUND:Teachers, as professional voice users, are at particular risk of voice disorders. Among contributing factors, stress and psychological tension could play a role but epidemiological data on this problem are scarce. The aim of this study was to evaluate prevalence and cofactors of voice disorders among teachers in the French National Education system, with particular attention paid to the association between voice complaint and psychological status.METHODS:The source data come from an epidemiological postal survey on physical and mental health conducted in a sample of 20,099 adults (in activity or retired) selected at random from the health plan records of the national education system. Overall response rate was 53%. Of the 10,288 respondents, 3,940 were teachers in activity currently giving classes to students. In the sample of those with complete data (n = 3,646), variables associated with voice disorders were investigated using logistic regression models. Studied variables referred to demographic characteristics, socio-professional environment, psychological distress, mental health disorders (DSM-IV), and sick leave.RESULTS:One in two female teachers reported voice disorders (50.0%) compared to one in four males (26.0%). Those who reported voice disorders presented higher level of psychological distress. Sex- and age-adjusted odds ratios [95% confidence interval] were respectively 1.8 [1.5-2.2] for major depressive episode, 1.7 [1.3-2.2] for general anxiety disorder, and 1.6 [1.2-2.2] for phobia. A significant association between voice disorders and sick leave was also demonstrated (1.5 [1.3-1.7]).CONCLUSION:Voice disorders were frequent among French teachers. Associations with psychiatric disorders suggest that a situation may exist which is more complex than simple mechanical failure. Further longitudinal research is needed to clarify the comorbidity between voice and psychological disorders

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Are we under-utilizing the talents of primary care personnel? A job analytic examination

BACKGROUND: Primary care staffing decisions are often made unsystematically, potentially leading to increased costs, dissatisfaction, turnover, and reduced quality of care. This article aims to (1) catalogue the domain of primary care tasks, (2) explore the complexity associated with these tasks, and (3) examine how tasks performed by different job titles differ in function and complexity, using Functional Job Analysis to develop a new tool for making evidence-based staffing decisions. METHODS: Seventy-seven primary care personnel from six US Department of Veterans Affairs (VA) Medical Centers, representing six job titles, participated in two-day focus groups to generate 243 unique task statements describing the content of VA primary care. Certified job analysts rated tasks on ten dimensions representing task complexity, skills, autonomy, and error consequence. Two hundred and twenty-four primary care personnel from the same clinics then completed a survey indicating whether they performed each task. Tasks were catalogued using an adaptation of an existing classification scheme; complexity differences were tested via analysis of variance. RESULTS: Objective one: Task statements were categorized into four functions: service delivery (65%), administrative duties (15%), logistic support (9%), and workforce management (11%). Objective two: Consistent with expectations, 80% of tasks received ratings at or below the mid-scale value on all ten scales. Objective three: Service delivery and workforce management tasks received higher ratings on eight of ten scales (multiple functional complexity dimensions, autonomy, human error consequence) than administrative and logistic support tasks. Similarly, tasks performed by more highly trained job titles received higher ratings on six of ten scales than tasks performed by lower trained job titles. Contrary to expectations, the distribution of tasks across functions did not significantly vary by job title. CONCLUSION: Primary care personnel are not being utilized to the extent of their training; most personnel perform many tasks that could reasonably be performed by personnel with less training. Primary care clinics should use evidence-based information to optimize job-person fit, adjusting clinic staff mix and allocation of work across staff to enhance efficiency and effectiveness

Climate change and outdoor regional living plant collections: an example from mainland Portugal

Original PaperClimate change threatens not only plant species occurring naturally, but also impacts on regional living plant collections, which play an important role in ex situ conservation strategies. In the last few years, several global circulation models have been used to predict different global climate change scenarios. Due to their coarse resolutions, and while more detailed regional approaches are not available, downscaling techniques have been proposed, as a very simple first approach to increase detail. We analysed seven sites on mainland Portugal with potential for species conservation (four botanic gardens and three universities), in the light of downscaled climate change scenarios, using an environmental envelope approach and a predefined bioclimatic neighbourhood for each site. Thresholds for the bioclimatic neighbourhood were based on Rivas-Martı´nez’s Bioclimatic Classification of the Earth. For each site, the expected geographical shift of its original bioclimatic neighbourhood (1950–2000) was mapped for 2020, 2050 and 2080. Analysing those shifts enabled us to delineate knowledge-transfer paths between sites, according to the analysed scenarios. We concluded that, according to the Intergovernmental Panel on Climate Change A2 scenario, all considered sites will be outside the predefined bioclimatic neighbourhood by 2080, while according to the B2 scenario all of them will be inside that neighbourhood, although sometimes marginally so. Therefore, the implementation of global sustainability measures as considered in the B2 scenario family can be of great importance in order to delay significantly the impacts of climate change, giving extra time for the adaptation of the outdoor regional living plant collectionsinfo:eu-repo/semantics/publishedVersio

A Study of B0 -> J/psi K(*)0 pi+ pi- Decays with the Collider Detector at Fermilab

We report a study of the decays B0 -> J/psi K(*)0 pi+ pi-, which involve the creation of a u u-bar or d d-bar quark pair in addition to a b-bar -> c-bar(c s-bar) decay. The data sample consists of 110 1/pb of p p-bar collisions at sqrt{s} = 1.8 TeV collected by the CDF detector at the Fermilab Tevatron collider during 1992-1995. We measure the branching ratios to be BR(B0 -> J/psi K*0 pi+ pi-) = (8.0 +- 2.2 +- 1.5) * 10^{-4} and BR(B0 -> J/psi K0 pi+ pi-) = (1.1 +- 0.4 +- 0.2) * 10^{-3}. Contributions to these decays are seen from psi(2S) K(*)0, J/psi K0 rho0, J/psi K*+ pi-, and J/psi K1(1270)

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

Quality of life after stroke: Evaluation of the Greek SAQOL-39g

Background/Aims: Stroke and aphasia rehabilitation aims to improve people’s quality of life. Yet, scales for measuring health-related quality of life in stroke typically exclude people with aphasia. They are also primarily available in English. An exception is the Stroke and Aphasia Quality of Life scale (SAQOL-39g). This scale has been tested with people with aphasia; it has been adapted for use in many countries including Greece. The aim of this study was to examine the psychometric properties of the Greek SAQOL-39g. Methods: An interview-based psychometric study was carried out. Participants completed: receptive sub-tests of Frenchay Aphasia Screening Test, Greek SAQOL-39g, General Health Questionnaire-12, Frenchay Activities Index, Montreal Cognitive Assessment and Barthel Index. Results: 86 people took part; 26 provided test-retest reliability data. The Greek SAQOL-39g demonstrated excellent acceptability (minimal missing data; no floor/ceiling effects), test-retest reliability (ICC= 0.96 scale, 0.83-0.99 domains) and internal consistency (Cronbach’s alpha 0.96 scale, 0.92-0.96 domains). There was strong evidence for convergent (r=0.53-0.80 scale; 0.54-0.89 domains) and discriminant validity (r=0.52 scale; 0.04-0.48 domains). Conclusion: The Greek SAQOL-39g is a valid and reliable scale. It is a promising measure for use in stroke and aphasia treatment prioritization, outcome measurement and service evaluation