Of flies, mice and men: a systematic approach to understanding the early life origins of chronic lung disease.

Despite intensive research efforts, the aetiology of the majority of chronic lung diseases (CLD) in both, children and adults, remains elusive. Current therapeutic options are limited, providing only symptomatic relief, rather than treating the underlying condition, or preventing its development in the first place. Thus, there is a strong and unmet clinical need for the development of both, novel effective therapies and preventative strategies for CLD. Many studies suggest that modifications of prenatal and/or early postnatal lung development will have important implications for future lung function and risk of CLD throughout life. This view represents a fundamental change of current pathophysiological concepts and treatment paradigms, and holds the potential to develop novel preventative and/or therapeutic strategies. However, for the successful development of such approaches, key questions, such as a clear understanding of underlying mechanisms of impaired lung development, the identification and validation of relevant preclinical models to facilitate translational research, and the development of concepts for correction of aberrant development, all need to be solved. Accordingly, a European Science Foundation Exploratory Workshop was held where clinical, translational and basic research scientists from different disciplines met to discuss potential mechanisms of developmental origins of CLD, and to identify major knowledge gaps in order to delineate a roadmap for future integrative research.

Material and Construction Optimization for Prevention of Premature Pavement Distress in PCC Pavements, Phase III Final Report, 2008

Mixture materials, mix design, and pavement construction are not isolated steps in the concrete paving process. Each affects the other in ways that determine overall pavement quality and long-term performance. However, equipment and procedures commonly used to test concrete materials and concrete pavements have not changed in decades, leaving gaps in our ability to understand and control the factors that determine concrete durability. The concrete paving community needs tests that will adequately characterize the materials, predict interactions, and monitor the properties of the concrete. The overall objectives of this study are (1) to evaluate conventional and new methods for testing concrete and concrete materials to prevent material and construction problems that could lead to premature concrete pavement distress and (2) to examine and refine a suite of tests that can accurately evaluate concrete pavement properties. The project included three phases. In Phase I, the research team contacted each of 16 participating states to gather information about concrete and concrete material tests. A preliminary suite of tests to ensure long-term pavement performance was developed. The tests were selected to provide useful and easy-to-interpret results that can be performed reasonably and routinely in terms of time, expertise, training, and cost. The tests examine concrete pavement properties in five focal areas critical to the long life and durability of concrete pavements: (1) workability, (2) strength development, (3) air system, (4) permeability, and (5) shrinkage. The tests were relevant at three stages in the concrete paving process: mix design, preconstruction verification, and construction quality control. In Phase II, the research team conducted field testing in each participating state to evaluate the preliminary suite of tests and demonstrate the testing technologies and procedures using local materials. A Mobile Concrete Research Lab was designed and equipped to facilitate the demonstrations. This report documents the results of the 16 state projects. Phase III refined and finalized lab and field tests based on state project test data. The results of the overall project are detailed herein. The final suite of tests is detailed in the accompanying testing guide.

A Thermokinetic approach to radiative heat transfer at the nanoscale

Radiative heat exchange at the nanoscale presents a challenge for several areas due to its scope and nature. Here, we provide a thermokinetic description of microscale radiative energy transfer including phonon-photon coupling manifested through a non-Debye relaxation behavior. We show that a lognormal-like distribution of modes of relaxation accounts for this non-Debye relaxation behavior leading to the thermal conductance. We also discuss the validity of the fluctuation-dissipation theorem. The general expression for the thermal conductance we obtain fits existing experimental results with remarkable accuracy. Accordingly, our approach offers an overall explanation of radiative energy transfer through micrometric gaps regardless of geometrical configurations and distances.

Impact of Left-Turn Phasing on Older and Younger Drivers at High-Speed Signalized Intersections, 2004

Several recent studies have demonstrated differences in safety between different types of left-turn phasing—protected, permitted, and protected/permitted phasing. The issue in question is whether older and younger drivers are more affected by a particular type of left-turn phasing at high-speed signalized intersections and whether they are more likely to contribute to a left-turn related crash under a specific type of left-turn phasing. This study evaluated the impact of different types of left-turn phasing on older and younger drivers at high-speed signalized intersections in Iowa. High-speed signalized intersections were of interest since oncoming speeds and appropriate gaps may be more difficult to judge for older drivers and those with less experience. A total of 101 intersections from various urban locations in Iowa with at least one intersecting roadway with a posted speed limit of 45 mph or higher were evaluated. Left-turn related crashes from 2001 to 2003 were evaluated. Left-turn crash rate and severity for young drivers (14- to 24-year-old), middle-age drivers (25- to 64-year-old), and older drivers (65 years and older) were calculated. Poisson regression was used to analyze left-turn crash rates by age group and type of phasing. Overall, left-turn crash rates indicated that protected phasing is much safer than protected/permitted and permitted phasing. Protected/permitted phasing had the highest left-turn crash rates overall.

Promotion of learning skills in the study of economics. pilot project in the subject area of

This communication is part of a larger teaching innovation project financed by the University ofBarcelona, whose objective is to develop and evaluate transversal competences of the UB, learningability and responsibility. The competence is divided into several sub-competencies being the ability toanalyze and synthesis the most intensely worked in the first year. The work presented here part fromthe results obtained in phase 1 and 2 previously implemented in other subjects (Mathematics andHistory) in the first year of the degree of Business Administration Degree. In these subjects’ previousexperiences there were deficiencies in the acquisition of learning skills by the students. The work inthe subject of Mathematics facilitated that students become aware of the deficit. The work on thesubject of History insisted on developing readings schemes and with the practical exercises wassought to go deeply in the development of this competence.The third phase presented here is developed in the framework of the second year degree, in the WorldEconomy subject. The objective of this phase is the development and evaluation of the same crosscompetence of the previous phases, from a practice that includes both, quantitative analysis andcritical reflection. Specifically the practice focuses on the study of the dynamic relationship betweeneconomic growth and the dynamics in the distribution of wealth. The activity design as well as theselection of materials to make it, has been directed to address gaps in the ability to analyze andsynthesize detected in the subjects of the first year in the previous phases of the project.The realization of the practical case is considered adequate methodology to improve the acquisition ofcompetence of the students, then it is also proposed how to evaluate the acquisition of suchcompetence. The practice is evaluated based on a rubric developed in the framework of the projectobjectives. Thus at the end of phase 3 we can analyze the process that have followed the students,detect where they have had major difficulties and identify those aspects of teaching that can help toimprove the acquisition of skills by the students. The interest of this phase resides in the possibility tovalue whether tracing of learning through competences, organized in a collaborative way, is a goodtool to develop the acquisition of these skills and facilitate their evaluation.

Identifying the unmet health needs of patients with congenital hypogonadotropic hypogonadism using a web-based needs assessment: implications for online interventions and peer-to-peer support.

BACKGROUND: Patients with rare diseases such as congenital hypogonadotropic hypogonadism (CHH) are dispersed, often challenged to find specialized care and face other health disparities. The internet has the potential to reach a wide audience of rare disease patients and can help connect patients and specialists. Therefore, this study aimed to: (i) determine if web-based platforms could be effectively used to conduct an online needs assessment of dispersed CHH patients; (ii) identify the unmet health and informational needs of CHH patients and (iii) assess patient acceptability regarding patient-centered, web-based interventions to bridge shortfalls in care. METHODS: A sequential mixed-methods design was used: first, an online survey was conducted to evaluate health promoting behavior and identify unmet health and informational needs of CHH men. Subsequently, patient focus groups were held to explore specific patient-identified targets for care and to examine the acceptability of possible online interventions. Descriptive statistics and thematic qualitative analyses were used. RESULTS: 105 male participants completed the online survey (mean age 37 ± 11, range 19-66 years) representing a spectrum of patients across a broad socioeconomic range and all but one subject had adequate healthcare literacy. The survey revealed periods of non-adherence to treatment (34/93, 37%) and gaps in healthcare (36/87, 41%) exceeding one year. Patient focus groups identified lasting psychological effects related to feelings of isolation, shame and body-image concerns. Survey respondents were active internet users, nearly all had sought CHH information online (101/105, 96%), and they rated the internet, healthcare providers, and online community as equally important CHH information sources. Focus group participants were overwhelmingly positive regarding online interventions/support with links to reach expert healthcare providers and for peer-to-peer support. CONCLUSION: The web-based needs assessment was an effective way to reach dispersed CHH patients. These individuals often have long gaps in care and struggle with the psychosocial sequelae of CHH. They are highly motivated internet users seeking information and tapping into online communities and are receptive to novel web-based interventions addressing their unmet needs.

Land plants and DNA barcodes: short-term and long-term goals.

Land plants have had the reputation of being problematic for DNA barcoding for two general reasons: (i) the standard DNA regions used in algae, animals and fungi have exceedingly low levels of variability and (ii) the typically used land plant plastid phylogenetic markers (e.g. rbcL, trnL-F, etc.) appear to have too little variation. However, no one has assessed how well current phylogenetic resources might work in the context of identification (versus phylogeny reconstruction). In this paper, we make such an assessment, particularly with two of the markers commonly sequenced in land plant phylogenetic studies, plastid rbcL and internal transcribed spacers of the large subunits of nuclear ribosomal DNA (ITS), and find that both of these DNA regions perform well even though the data currently available in GenBank/EBI were not produced to be used as barcodes and BLAST searches are not an ideal tool for this purpose. These results bode well for the use of even more variable regions of plastid DNA (such as, for example, psbA-trnH) as barcodes, once they have been widely sequenced. In the short term, efforts to bring land plant barcoding up to the standards being used now in other organisms should make swift progress. There are two categories of DNA barcode users, scientists in fields other than taxonomy and taxonomists. For the former, the use of mitochondrial and plastid DNA, the two most easily assessed genomes, is at least in the short term a useful tool that permits them to get on with their studies, which depend on knowing roughly which species or species groups they are dealing with, but these same DNA regions have important drawbacks for use in taxonomic studies (i.e. studies designed to elucidate species limits). For these purposes, DNA markers from uniparentally (usually maternally) inherited genomes can only provide half of the story required to improve taxonomic standards being used in DNA barcoding. In the long term, we will need to develop more sophisticated barcoding tools, which would be multiple, low-copy nuclear markers with sufficient genetic variability and PCR-reliability; these would permit the detection of hybrids and permit researchers to identify the 'genetic gaps' that are useful in assessing species limits.

The effect of scale in daily precipitation hazard assessment

Daily precipitation is recorded as the total amount of water collected by a rain-gauge in 24 h. Events are modelled as a Poisson process and the 24 h precipitation by a Generalised Pareto Distribution (GPD) of excesses. Hazard assessment is complete when estimates of the Poisson rate and the distribution parameters, together with a measure of their uncertainty, are obtained. The shape parameter of the GPD determines the support of the variable: Weibull domain of attraction (DA) corresponds to finite support variables as should be for natural phenomena. However, Fréchet DA has been reported for daily precipitation, which implies an infinite support and a heavy-tailed distribution. Bayesian techniques are used to estimate the parameters. The approach is illustrated with precipitation data from the Eastern coast of the Iberian Peninsula affected by severe convective precipitation. The estimated GPD is mainly in the Fréchet DA, something incompatible with the common sense assumption of that precipitation is a bounded phenomenon. The bounded character of precipitation is then taken as a priori hypothesis. Consistency of this hypothesis with the data is checked in two cases: using the raw-data (in mm) and using log-transformed data. As expected, a Bayesian model checking clearly rejects the model in the raw-data case. However, log-transformed data seem to be consistent with the model. This fact may be due to the adequacy of the log-scale to represent positive measurements for which differences are better relative than absolute

Impact of engineered nanomaterials on health : considerations for benefit-risk assessment

Nanotechnology encompasses the design, characterisation, production and application of materials and systems by controlling shape and size at the nanoscale (nanometres). Nanomaterials may differ from other materials because of their relatively large specific surface area, such that surface properties become particularly important. There has been rapid growth in investment in nanotechnology by both the public and private sectors worldwide. In the EU, nanotechnology is expected to become an important strategic contributor to achieving economic gain and societal and individual benefits. At the same time there is continuing scientific uncertainty and controversy about the safety of nanomaterials. It is important to ensure that timely policy development takes this into consideration. Uncertainty about safety may lead to polarised public debate and to business unwillingness to invest further. A clear regulatory framework to address potential health and environmental impacts, within the wider context of evaluating and communicating the benefit-risk balance, must be a core part of Europe's integrated efforts for nanotechnology innovation. While a number of studies have been carried out on the effect of environmental nanoparticles, e.g. from combustion processes, on human health, there is yet no generally acceptable paradigm for safety assessment of nanomaterials in consumer and other products. Therefore, a working group was established to consider issues for the possible impact of nanomaterials on human health focussing specifically on engineered nanomaterials. This represents the first joint initiative between EASAC and the Joint Research Centre of the European Commission. The working group was given the remit to describe the state of the art of benefits and potential risks, current methods for safety assessment, and to evaluate their relevance, identify knowledge gaps in studying the safety of current nanomaterials, and recommend on priorities for nanomaterial research and the regulatory framework. This report focuses on key principles and issues, cross-referencing other sources for detailed information, rather than attempting a comprehensive account of the science. The focus is on human health although environmental effects are also discussed when directly relevant to health

Sensitivity of Spring Phenology to Warming Across Temporal and Spatial Climate Gradients in Two Independent Databases

Disparate ecological datasets are often organized into databases post hoc and then analyzed and interpreted in ways that may diverge from the purposes of the original data collections. Few studies, however, have attempted to quantify how biases inherent in these data (for example, species richness, replication, climate) affect their suitability for addressing broad scientific questions, especially in under-represented systems (for example, deserts, tropical forests) and wild communities. Here, we quantitatively compare the sensitivity of species first flowering and leafing dates to spring warmth in two phenological databases from the Northern Hemisphere. One-PEP725-has high replication within and across sites, but has low species diversity and spans a limited climate gradient. The other-NECTAR-includes many more species and a wider range of climates, but has fewer sites and low replication of species across sites. PEP725, despite low species diversity and relatively low seasonality, accurately captures the magnitude and seasonality of warming responses at climatically similar NECTAR sites, with most species showing earlier phenological events in response to warming. In NECTAR, the prevalence of temperature responders significantly declines with increasing mean annual temperature, a pattern that cannot be detected across the limited climate gradient spanned by the PEP725 flowering and leafing data. Our results showcase broad areas of agreement between the two databases, despite significant differences in species richness and geographic coverage, while also noting areas where including data across broader climate gradients may provide added value. Such comparisons help to identify gaps in our observations and knowledge base that can be addressed by ongoing monitoring and research efforts. Resolving these issues will be critical for improving predictions in understudied and under-sampled systems outside of the temperature seasonal mid-latitudes.

Structural, metamorphic and geochronological relations between the Zanskar Shear Zone and the Miyar Shear Zone (NW Indian Himalaya): Evidence for two distinct tectonic structures and implications for the evolution of the High Himalayan Crystalline of Zanskar

The geologic structures and metamorphic zonation of the northwestern Indian Himalaya contrast significantly with those in the central and eastern parts of the range, where the high-grade metamorphic rocks of the High Himalayan Crystalline (HHC) thrust southward over the weakly metamorphosed sediments of the Lesser Himalaya along the Main Central Thrust (MCT). Indeed, the hanging wall of the MCT in the NW Himalaya mainly consists of the greenschist facies metasediments of the Chamba zone, whereas HHC high-grade rocks are exposed more internally in the range as a large-scale dome called the Gianbul dome. This Gianbul dome is bounded by two oppositely directed shear zones, the NE-dipping Zanskar Shear Zone (ZSZ) on the northern flank and the SW-dipping Miyar Shear Zone (MSZ) on the southern limb. Current models for the emplacement of the HHC in NW India as a dome structure differ mainly in terms of the roles played by both the ZSZ and the MSZ during the tectonothermal evolution of the HHC. In both the channel flow model and wedge extrusion model, the ZSZ acts as a backstop normal fault along which the high-grade metamorphic rocks of the HHC of Zanskar are exhumed. In contrast, the recently proposed tectonic wedging model argues that the ZSZ and the MSZ correspond to one single detachment system that operates as a subhorizontal backthrust off of the MCT. Thus, the kinematic evolution of the two shear zones, the ZSZ and the MSZ, and their structural, metamorphic and chronological relations appear to be diagnostic features for discriminating the different models. In this paper, structural, metamorphic and geochronological data demonstrate that the MSZ and the ZSZ experienced two distinct kinematic evolutions. As such, the data presented in this paper rule out the hypothesis that the MSZ and the ZSZ constitute one single detachment system, as postulated by the tectonic wedging model. Structural, metamorphic and geochronological data are used to present an alternative tectonic model for the large-scale doming in the NW Indian Himalaya involving early NE-directed tectonics, weakness in the upper crust, reduced erosion at the orogenic front and rapid exhumation along both the ZSZ and the MSZ.

Safety concerns about CCR5 as an antiviral target.

PURPOSE OF REVIEW: Clinical trials of CCR5 antagonists attest to their efficacy and tolerance in HIV treatment. However, there has been debate on their long-term safety because of the role of CCR5 in innate immunity. This review highlights gaps in our understanding of epidemiology of infections that are modulated by CCR5, in particular, in HIV-infected individuals. RECENT FINDINGS: In the mouse model, CCR5 has a role in the response against pathogens as diverse as Toxoplama gondii, West Nile virus, Mycobacterium tuberculosis, herpes simplex virus, Trypanosoma cruzi, Cryptococcus neoformans, Chlamydia trachomatis, Listeria, and plasmodia. In human cohorts, individuals carrying the defective CCR5Delta32 allele present an increased susceptibility to flavivirus (West Nile virus and tickborne encephalitis virus). The selective pressures that led to the spread of loss-of-function CCR5 mutations in humans (CCR5Delta32), and in mangabeys (CCR5Delta24) are not understood. SUMMARY: The recent availability of CCR5 antagonists has raised concern that genetic, biological, or chemical CCR5 knockout, although beneficial against some pathogens (i.e. HIV), could be deleterious for other processes implicated in pathogen response. The consequences of long-term pharmaceutical intervention on CCR5 should be carefully assessed through rigorous postmarketing surveillance.

Ympäristötietämyksen hallintasovelluksen kehittäminen

Uudistunut ympäristölainsäädäntö vaatii energiantuotantolaitoksilta yhä enemmän järjestelmällistä ympäristötiedon hallintaa. LCP- ja jätteenpolttoasetuksen velvoitteet ovat asettaneet uusia vaatimuksia päästöjen valvontaan ja siihen käytettävien mittausjärjestelmien laadunvarmennukseen sekä päästötietojen raportointiin. Uudistukset ovat lisänneet huomattavasti laitoksilla ympäristötiedon käsittelyyn kuluvaa aikaa. Laitosten toimintaehdot määritellään ympäristöviranomaisen myöntämässä ympäristöluvassa, joka on tärkein yksittäinen laitoksen toimintaa ohjaava tekijä. Tämän lisäksi monet toimijat haluavat parantaa ympäristöasioiden tasoaan vapaaehtoisilla ympäristöjärjestelmillä. Tässä diplomityössä kuvataan energiantuotantolaitosten ympäristöasioiden tallentamiseen ja hallintaan kehitetty selainpohjainen Metso Automationin DNAecoDiary'sovellus. Työ on rajattu koskemaan Suomessa toimivia LCP- ja/tai jätteenpolttoasetuksen alaisia laitoksia. Sovelluksen avulla voidaan varmistaa energiantuotantolaitosten poikkeamien, häiriöilmoitusten, päästömittalaitteisiin liittyvien tapahtumien ja muun ympäristöasioiden valvontaan liittyvän informaation tehokas hallinta. Sovellukseen tallennetaan ympäristötapahtumiin liittyvät perustiedot sekä etenkin käyttäjien tapahtumiin liittyvä kokemustietämys. Valvontakirjaukseen voidaan liittää tapahtuman perustietojen lisäksi myös tiedostoja ja kuvia. Sovellusta ja sillä kerättyä tietoa voidaan hyödyntää laitoksella käsilläolevien ongelmien ratkaisuun, ympäristötapahtumien todentamiseen sekä ympäristöraporttien laadintaan. Kehitystyön tueksi järjestettiin asiakastarvekartoitus, jonka perusteella ideoitiin sovelluksen ominaisuuksia. Tässä työssä on esitetty ympäristötiedon hallinan perusteet, selvitetty DNAecoDiaryn toimintaperiaatteet ja annettu esimerkkejä sen hyödyntämisestä. Sovelluksen lopullinen sisältö määritellään kunkin asiakkaan ympäristöluvan ja oma-valvonnan tarpeiden mukaisesti. Sovellus toimii itsenäisesti tai osana laajempaa Metso Automationin päästöjenhallinta- ja raportointisovelluskokonaisuutta.

Modeling competencies and capabilities in knowledge intensive business environment

Tämän diplomityön päämääränä oli tutkia Perloksen teknologiaosaamisia. Perloksen tavoitteena on tulevaisuudessa yhdistää ja soveltaa uusia teknologioita ja älykkäitä materiaaleja muovimekaniikkaan.Ideana oli mallintaa Perloksen osaamisia ja osaamisgapeja ottaen huomioon heidän tulevaisuuden visionsa. Projektituotteena osaamisten mallintamisessa oli Perlos Healthcaren asiakkaan analysoiva mittauslaite. Tutkimuksen arvo on huomattava sillä tunnistamalla osaamisensa ja kyvykkyytensä yritys pystyy luomaan paremman tarjooman vastatessaan koko ajan kasvaviin asiakasvaatimuksiin. Tutkimus on osa TEKESin rahoittamaa LIIMA -projektia. Työn ensimmäisessä osassa esitellään osaamiseen ja partneroitumiseen liittyviä teorioita. Osaamisten mallintaminen tehtiin Excel -pohjaisella työkalulla. Se sisältää projektituotteeseen liittyen osaamisriippuvuuksien mallintamisen ja gap -analyysin. Yhtenä tutkimusmetodina käytettiin haastattelututkimusta. Työ ja sen tulokset antavat operatiivista hyötyä teknologioiden ja markkinoiden välisessä kentässä.

Systematic review protocol to define classical IgE-associated diseases from birth to adolescence: the MeDALL study

BACKGROUND: Classical disease phenotypes are mainly based on descriptions of symptoms and the hypothesis that a given pattern of symptoms provides a diagnosis. With refined technologies there is growing evidence that disease expression in patients is much more diverse and subtypes need to be defined to allow a better targeted treatment. One of the aims of the Mechanisms of the Development of Allergy Project (MeDALL,FP7) is to re-define the classical phenotypes of IgE-associated allergic diseases from birth to adolescence, by consensus among experts using a systematic review of the literature and identify possible gaps in research for new disease markers. This paper describes the methods to be used for the systematic review of the classical IgE-associated phenotypes applicable in general to other systematic reviews also addressing phenotype definitions based on evidence. METHODS/DESIGN: Eligible papers were identified by PubMed search (complete database through April 2011). This search yielded 12,043 citations. The review includes intervention studies (randomized and clinical controlled trials) and observational studies (cohort studies including birth cohorts, case-control studies) as well as case series. Systematic and non-systematic reviews, guidelines, position papers and editorials are not excluded but dealt with separately. Two independent reviewers in parallel conducted consecutive title and abstract filtering scans. For publications where title and abstract fulfilled the inclusion criteria the full text was assessed. In the final step, two independent reviewers abstracted data using a pre-designed data extraction form with disagreements resolved by discussion among investigators. DISCUSSION: The systematic review protocol described here allows to generate broad,multi-phenotype reviews and consensus phenotype definitions. The in-depth analysis of the existing literature on the classification of IgE-associated allergic diseases through such a systematic review will 1) provide relevant information on the current epidemiologic definitions of allergic diseases, 2) address heterogeneity and interrelationships and 3) identify gaps in knowledge.