Validity of low-contrast letter acuity as a visual performance outcome measure for multiple sclerosis.

Low-contrast letter acuity (LCLA) has emerged as the leading outcome measure to assess visual disability in multiple sclerosis (MS) research. As visual dysfunction is one of the most common manifestations of MS, sensitive visual outcome measures are important in examining the effect of treatment. Low-contrast acuity captures visual loss not seen in high-contrast visual acuity (HCVA) measurements. These issues are addressed by the MS Outcome Assessments Consortium (MSOAC), including representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS. MSOAC goals are acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful to persons with MS. A critical step is elucidation of clinically relevant benchmarks, well-defined degrees of disability, and gradients of change that are clinically meaningful. This review shows that MS and disease-free controls have similar median HCVA, while MS patients have significantly lower LCLA. Deficits in LCLA and vision-specific quality of life are found many years after an episode of acute optic neuritis, even when HCVA has recovered. Studies reveal correlations between LCLA and the Expanded Disability Status Score (EDSS), Multiple Sclerosis Functional Composite (MSFC), retinal nerve fiber layer (RNFL) and ganglion cell layer plus inner plexiform layer (GCL + IPL) thickness on optical coherence tomography (OCT), brain magnetic resonance imaging (MRI), visual evoked potential (VEP), electroretinogram (ERG), pupillary function, and King-Devick testing. This review also concludes that a 7-point change in LCLA is clinically meaningful. The overall goal of this review is to describe and characterize the LCLA metric for research and clinical use among persons with MS

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr

Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia

BackgroundCritical limb ischemia (CLI) constitutes the most aggressive form of peripheral arterial occlusive disease, characterized by the blockade of arteries supplying blood to the lower extremities, significantly diminishing oxygen and nutrient supply. CLI patients usually undergo amputation of fingers, feet, or extremities, with a high risk of mortality due to associated comorbidities.Circulating angiogenic cells (CACs), also known as early endothelial progenitor cells, constitute promising candidates for cell therapy in CLI due to their assigned vascular regenerative properties. Preclinical and clinical assays with CACs have shown promising results. A better understanding of how these cells participate in vascular regeneration would significantly help to potentiate their role in revascularization.Herein, we analyzed the initial molecular mechanisms triggered by human CACs after being administered to a murine model of CLI, in order to understand how these cells promote angiogenesis within the ischemic tissues.MethodsBalb-c nude mice (n:24) were distributed in four different groups: healthy controls (C, n:4), shams (SH, n:4), and ischemic mice (after femoral ligation) that received either 50 mu l physiological serum (SC, n:8) or 5x10(5) human CACs (SE, n:8). Ischemic mice were sacrificed on days 2 and 4 (n:4/group/day), and immunohistochemistry assays and qPCR amplification of Alu-human-specific sequences were carried out for cell detection and vascular density measurements. Additionally, a label-free MS-based quantitative approach was performed to identify protein changes related.ResultsAdministration of CACs induced in the ischemic tissues an increase in the number of blood vessels as well as the diameter size compared to ischemic, non-treated mice, although the number of CACs decreased within time. The initial protein changes taking place in response to ischemia and more importantly, right after administration of CACs to CLI mice, are shown.ConclusionsOur results indicate that CACs migrate to the injured area; moreover, they trigger protein changes correlated with cell migration, cell death, angiogenesis, and arteriogenesis in the host. These changes indicate that CACs promote from the beginning an increase in the number of vessels as well as the development of an appropriate vascular network.Institute of Health Carlos III, ISCIII; Junta de Andaluci

Small Polarons in Transition Metal Oxides

The formation of polarons is a pervasive phenomenon in transition metal oxide compounds, with a strong impact on the physical properties and functionalities of the hosting materials. In its original formulation the polaron problem considers a single charge carrier in a polar crystal interacting with its surrounding lattice. Depending on the spatial extension of the polaron quasiparticle, originating from the coupling between the excess charge and the phonon field, one speaks of small or large polarons. This chapter discusses the modeling of small polarons in real materials, with a particular focus on the archetypal polaron material TiO2. After an introductory part, surveying the fundamental theoretical and experimental aspects of the physics of polarons, the chapter examines how to model small polarons using first principles schemes in order to predict, understand and interpret a variety of polaron properties in bulk phases and surfaces. Following the spirit of this handbook, different types of computational procedures and prescriptions are presented with specific instructions on the setup required to model polaron effects.Comment: 36 pages, 12 figure

Toward the definition of efficacy and safety criteria for advancing gene drive-modified mosquitoes to field testing

Mosquitoes containing gene drive systems are being developed as complementary tools to prevent transmission of malaria and other mosquito-borne diseases. As with any new tool, decision makers and other stakeholders will need to balance risks (safety) and benefits (efficacy) when considering the rationale for testing and deploying gene drive-modified mosquito products. Developers will benefit from standards for judging whether an investigational gene drive product meets acceptability criteria for advancing to field trials. Such standards may be formalized as preferred product characteristics and target product profiles, which describe the desired attributes of the product category and of a particular product, respectively. This report summarizes discussions from two scientific workshops aimed at identifying efficacy and safety characteristics that must be minimally met for an investigational gene drive-modified mosquito product to be deemed viable to move from contained testing to field release and the data that will be needed to support an application for first field release

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

The Lung Screen Uptake Trial (LSUT): protocol for a randomised controlled demonstration lung cancer screening pilot testing a targeted invitation strategy for high risk and ‘hard-to-reach’ patients

Background Participation in low-dose CT (LDCT) lung cancer screening offered in the trial context has been poor, especially among smokers from socioeconomically deprived backgrounds; a group for whom the risk-benefit ratio is improved due to their high risk of lung cancer. Attracting high risk participants is essential to the success and equity of any future screening programme. This study will investigate whether the observed low and biased uptake of screening can be improved using a targeted invitation strategy. Methods/design A randomised controlled trial design will be used to test whether targeted invitation materials are effective at improving engagement with an offer of lung cancer screening for high risk candidates. Two thousand patients aged 60–75 and recorded as a smoker within the last five years by their GP, will be identified from primary care records and individually randomised to receive either intervention invitation materials (which take a targeted, stepped and low burden approach to information provision prior to the appointment) or control invitation materials. The primary outcome is uptake of a nurse-led ‘lung health check’ hospital appointment, during which patients will be offered a spirometry test, an exhaled carbon monoxide (CO) reading, and an LDCT if eligible. Initial data on demographics (i.e. age, sex, ethnicity, deprivation score) and smoking status will be collected in primary care and analysed to explore differences between attenders and non-attenders with respect to invitation group. Those who attend the lung health check will have further data on smoking collected during their appointment (including pack-year history, nicotine dependence and confidence to quit). Secondary outcomes will include willingness to be screened, uptake of LDCT and measures of informed decision-making to ensure the latter is not compromised by either invitation strategy. Discussion If effective at improving informed uptake of screening and reducing bias in participation, this invitation strategy could be adopted by local screening pilots or a national programme. Trial registration This study was registered with the ISRCTN (International Standard Registered Clinical/soCial sTudy Number : ISRCTN21774741) on the 23rd September 2015 and the NIH ClinicalTrials.gov database (NCT0255810) on the 22nd September 2015

Convective self-aggregation in numerical simulations: a review

Organized convection in the Tropics occurs across a range of spatial and temporal scales and strongly influences cloud cover and humidity. One mode of organization found is “self-aggregation”, in which moist convection spontaneously organizes into one or several isolated clusters despite spatially homogeneous boundary conditions and forcing. Self-aggregation is driven by interactions between clouds, moisture, radiation, surface fluxes, and circulation, and occurs in a wide variety of idealized simulations of radiative-convective equilibrium. Here we provide a review of convective self-aggregation in numerical simulations, including its character, causes, and effects. We describe the evolution of self-aggregation including its time and length scales and the physical mechanisms leading to its triggering and maintenance, and we also discuss possible links to climate and climate change

Toward a Theory of Child Well-Being

Assuring the well-being of children has emerged over the past several decades as an important goal for health and social policymakers. Although the concept of child well-being has been operationalized and measured in different ways by different child-serving entities, there are few unifying theories that could undergird and inform these various conceptual and measurement efforts. In this paper, we attempt to construct a theory of child well-being. We first review the social and policy history of the concept of child well-being, and briefly review its measurement based on these conceptualizations. We then examine three types of theories of well-being extant in philosophy - mental states theories, desire-based theories and needs-based theories - and investigate their suitability to serve as prototypes of a theory of child well-being. We develop a constraint that child well-being is important in and of itself and not merely as a way station to future adult well-being (we call this a non-reduction constraint). Using this constraint, we identify the limitations of each of the three sets of theories to serve as a basis for a theory of child well-being. Based on a developmentalist approach, we then articulate a theory of child well-being that contains two conditions. First, a child's stage-appropriate capacities that equip her for successful adulthood, given her environment; and, second, an engagement with the world in child-appropriate ways. We conclude by reviewing seven implications of this theoretical approach for the measurement of child well-being. Key Words Child well-being, philosophy, social policy, child developmentNoneThis is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s11205-014-0665-

The time course of auditory and language-specific mechanisms in compensation for sibilant assimilation

Models of spoken-word recognition differ on whether compensation for assimilation is language-specific or depends on general auditory processing. English and French participants were taught words that began or ended with the sibilants /s/ and /∫/. Both languages exhibit some assimilation in sibilant sequences (e.g., /s/ becomes like [∫] in dress shop and classe chargée), but they differ in the strength and predominance of anticipatory versus carryover assimilation. After training, participants were presented with novel words embedded in sentences, some of which contained an assimilatory context either preceding or following. A continuum of target sounds ranging from [s] to [∫] was spliced into the novel words, representing a range of possible assimilation strengths. Listeners' perceptions were examined using a visual-world eyetracking paradigm in which the listener clicked on pictures matching the novel words. We found two distinct language-general context effects: a contrastive effect when the assimilating context preceded the target, and flattening of the sibilant categorization function (increased ambiguity) when the assimilating context followed. Furthermore, we found that English but not French listeners were able to resolve the ambiguity created by the following assimilatory context, consistent with their greater experience with assimilation in this context. The combination of these mechanisms allows listeners to deal flexibly with variability in speech forms