Downward shortwave surface irradiance from 17 sites for the FIRE/SRB Wisconsin experiment

A field experiment was conducted in Wisconsin during Oct. to Nov. 1986 for purposes of both intensive cirrus cloud measurments and SRB algorithm validation activities. The cirrus cloud measurements were part of the FIRE. Tables are presented which show data from 17 sites in the First ISCCP (International Satellite Cloud Climatology Project) Regional Experiment/Surface Radiation Budget (FIRE/SRB) Wisconsin experiment region. A discussion of intercomparison results and calibration inconsistencies is also included

Frequency and risk factors for prevalent, incident, and persistent genital carcinogenic human papillomavirus infection in sexually active women: community based cohort study

Objective To investigate frequency and risk factors for prevalent, incident, and persistent carcinogenic human papillomavirus (HPV) in young women before the introduction of immunisation against HPV types 16 and 18 for schoolgirls

Perspectives of people in Mali toward genetically-modified mosquitoes for malaria control

Background: Genetically-modified (GM) mosquitoes have been proposed as part of an integrated vector control strategy for malaria control. Public acceptance is essential prior to field trials, particularly since mosquitoes are a vector of human disease and genetically modified organisms (GMOs) face strong scepticism in developed and developing nations. Despite this, in sub-Saharan Africa, where the GM mosquito effort is primarily directed, very little data is available on perspectives to GMOs. Here, results are presented of a qualitative survey of public attitudes to GM mosquitoes for malaria control in rural and urban areas of Mali, West Africa between the months of October 2008 and June 2009. Methods: The sample consisted of 80 individuals - 30 living in rural communities, 30 living in urban suburbs of Bamako, and 20 Western-trained and traditional health professionals working in Bamako and Bandiagara. Questions were asked about the cause of malaria, heredity and selective breeding. This led to questions about genetic alterations, and acceptable conditions for a release of pest-resistant GM corn and malaria-refractory GM mosquitoes. Finally, participants were asked about the decision-making process in their community. Interviews were transcribed and responses were categorized according to general themes. Results: Most participants cited mosquitoes as one of several causes of malaria. The concept of the gene was not widely understood; however selective breeding was understood, allowing limited communication of the concept of genetic modification. Participants were open to a release of pest-resistant GM corn, often wanting to conduct a trial themselves. The concept of a trial was reapplied to GM mosquitoes, although less frequently. Participants wanted to see evidence that GM mosquitoes can reduce malaria prevalence without negative consequences for human health and the environment. For several participants, a mosquito control programme was preferred; however a transgenic release that satisfied certain requirements was usually acceptable. Conclusions: Although there were some dissenters, the majority of participants were pragmatic towards a release of GM mosquitoes. An array of social and cultural issues associated with malaria, mosquitoes and genetic engineering became apparent. If these can be successfully addressed, then social acceptance among the populations surveyed seems promising

A global map of dominant malaria vectors

Background: Global maps, in particular those based on vector distributions, have long been used to help visualise the global extent of malaria. Few, however, have been created with the support of a comprehensive and extensive evidence-based approach.\ud Methods: Here we describe the generation of a global map of the dominant vector species (DVS) of malaria that makes use of predicted distribution maps for individual species or species complexes.\ud Results: Our global map highlights the spatial variability in the complexity of the vector situation. In Africa, An. gambiae, An. arabiensis and An. funestus are co-dominant across much of the continent, whereas in the Asian- Pacific region there is a highly complex situation with multi-species coexistence and variable species dominance.\ud Conclusions: The competence of the mapping methodology to accurately portray DVS distributions is discussed. The comprehensive and contemporary database of species-specific spatial occurrence (currently available on request) will be made directly available via the Malaria Atlas Project (MAP) website from early 2012

The science of clinical practice: disease diagnosis or patient prognosis? Evidence about "what is likely to happen" should shape clinical practice.

BACKGROUND: Diagnosis is the traditional basis for decision-making in clinical practice. Evidence is often lacking about future benefits and harms of these decisions for patients diagnosed with and without disease. We propose that a model of clinical practice focused on patient prognosis and predicting the likelihood of future outcomes may be more useful. DISCUSSION: Disease diagnosis can provide crucial information for clinical decisions that influence outcome in serious acute illness. However, the central role of diagnosis in clinical practice is challenged by evidence that it does not always benefit patients and that factors other than disease are important in determining patient outcome. The concept of disease as a dichotomous 'yes' or 'no' is challenged by the frequent use of diagnostic indicators with continuous distributions, such as blood sugar, which are better understood as contributing information about the probability of a patient's future outcome. Moreover, many illnesses, such as chronic fatigue, cannot usefully be labelled from a disease-diagnosis perspective. In such cases, a prognostic model provides an alternative framework for clinical practice that extends beyond disease and diagnosis and incorporates a wide range of information to predict future patient outcomes and to guide decisions to improve them. Such information embraces non-disease factors and genetic and other biomarkers which influence outcome. SUMMARY: Patient prognosis can provide the framework for modern clinical practice to integrate information from the expanding biological, social, and clinical database for more effective and efficient care

H1N1 2009 Pandemic Influenza Virus: Resistance of the I223R Neuraminidase Mutant Explained by Kinetic and Structural Analysis

Two classes of antiviral drugs, neuraminidase inhibitors and adamantanes, are approved for prophylaxis and therapy against influenza virus infections. A major concern is that antiviral resistant viruses emerge and spread in the human population. The 2009 pandemic H1N1 virus is already resistant to adamantanes. Recently, a novel neuraminidase inhibitor resistance mutation I223R was identified in the neuraminidase of this subtype. To understand the resistance mechanism of this mutation, the enzymatic properties of the I223R mutant, together with the most frequently observed resistance mutation, H275Y, and the double mutant I223R/H275Y were compared. Relative to wild type, KMvalues for MUNANA increased only 2-fold for the single I223R mutant and up to 8-fold for the double mutant. Oseltamivir inhibition constants (KI) increased 48-fold in the single I223R mutant and 7500-fold in the double mutant. In both cases the change was largely accounted for by an increased dissociation rate constant for oseltamivir, but the inhibition constants for zanamivir were less increased. We have used X-ray crystallography to better understand the effect of mutation I223R on drug binding. We find that there is shrinkage of a hydrophobic pocket in the active site as a result of the I223R change. Furthermore, R223 interacts with S247 which changes the rotamer it adopts and, consequently, binding of the pentoxyl substituent of oseltamivir is not as favorable as in the wild type. However, the polar glycerol substituent present in zanamivir, which mimics the natural substrate, is accommodate

Vectorial capacity and vector control: reconsidering sensitivity to parameters for malaria elimination

Background: Major gains have been made in reducing malaria transmission in many parts of the world, principally by scaling-up coverage with long-lasting insecticidal nets and indoor residual spraying. Historically, choice of vector control intervention has been largely guided by a parameter sensitivity analysis of George Macdonald's theory of vectorial capacity that suggested prioritizing methods that kill adult mosquitoes. While this advice has been highly successful for transmission suppression, there is a need to revisit these arguments as policymakers in certain areas consider which combinations of interventions are required to eliminate malaria.Methods and Results: Using analytical solutions to updated equations for vectorial capacity we build on previous work to show that, while adult killing methods can be highly effective under many circumstances, other vector control methods are frequently required to fill effective coverage gaps. These can arise due to pre-existing or developing mosquito physiological and behavioral refractoriness but also due to additive changes in the relative importance of different vector species for transmission. Furthermore, the optimal combination of interventions will depend on the operational constraints and costs associated with reaching high coverage levels with each intervention.Conclusions: Reaching specific policy goals, such as elimination, in defined contexts requires increasingly non-generic advice from modelling. Our results emphasize the importance of measuring baseline epidemiology, intervention coverage, vector ecology and program operational constraints in predicting expected outcomes with different combinations of interventions.<br/

Identification of road user related risk factors, deliverable 4.1 of the H2020 project SafetyCube.

Safety CaUsation, Benefits and Efficiency (SafetyCube) is a European Commission supported Horizon 2020 project with the objective of developing an innovative road safety Decision Support System (DSS). The DSS will enable policy-makers and stakeholders to select and implement the most appropriate strategies, measures, and cost-effective approaches to reduce casualties of all road user types and all severities. This document is the first deliverable (4.1) of work package 4 which is dedicated to identifying and assessing human related risk factors and corresponding countermeasures as well as their effect on road safety. The focus of deliverable 4.1 is on identification and assessment of risk factors and describes the corresponding operational procedure and corresponding outcomes. The following steps have been carried out: Identification of human related risk factors – creation of a taxonomy Consultation of relevant stakeholders and policy papers for identification of topic with high priority (‘hot topics’) Systematic literature search and selection of relevant studies on identified risk factors •Coding of studies •Analysis of risk factors on basis of coded studies •Synopses of risk factors, including accident scenarios The core output of this task are synopses of risk factors which will be available through the DSS. Within the synopses, each risk factor was analysed systematically on basis of scientific studies and is further assigned to one of four levels of risk (marked with a colour code). Essential information of the more than 180 included studies were coded and will also be available in the database of the DSS. Furthermore, the synopses contain theoretical background on the risk factor and are prepared in different sections with different levels of detail for an academic as well as a non-academic audience. These sections are readable independently. It is important to note that the relationship between road safety and road user related risk factors is a difficult task. For some risk factors the available studies focused more on conditions of the behaviour (in which situations the behaviour is shown or which groups are more likely to show this behaviour) rather than the risk factor itself. Therefore, it cannot be concluded that those risk factors that have not often been studied or have to rely more indirect and arguably weaker methodologies, e.g. self-reports , do not increase the chance of a crash occurring. The following analysed risk factors were assessed as ‘risky’, ‘probably risky’ or ‘unclear’. No risk factors were identified as ‘probably not risky’. Risky Probably risky Unclear • Influenced driving – alcohol • Influenced Driving – drugs (legal & illegal) • Speeding and inappropriate speed • Traffic rule violations – red light running • Distraction – cell phone use (hand held) • Distraction – cell phone use (hands free) • Distraction – cell phone use (texting) • Fatigue – sleep disorders – sleep apnea • Risk taking – overtaking • Risk taking – close following behaviour • Insufficient knowledge and skills • Functional impairment – cognitive impairment • Functional impairment – vision loss • Diseases and disorders – diabetes • Personal factors – sensation seeking • Personal factors – ADHD • Emotions – anger, aggression • Fatigue – Not enough sleep/driving while tired • Distraction – conversation with passengers • Distraction – outside of vehicle • Distraction – cognitive overload and inattention • Functional impairment – hearing loss (few studies) • Observation errors (few studies) • Distraction – music – entertainment systems (many studies, mixed results) • Distraction – operating devices (many studies, mixed results) The next step in SafetyCube’s WP4 is to identify and assess the effectiveness of measures and to establish a link to the identified risk factors. The work of this first task indicates a set of risk factors that should be centre of attention when identifying corresponding road safety measures (category ‘risky’)

Identification and safety effects of road user related measures. Deliverable 4.2 of the H2020 project SafetyCube

Safety CaUsation, Benefits and Efficiency (SafetyCube) is a European Commission supported Horizon 2020 project with the objective of developing an innovative road safety Decision Support System (DSS). The DSS will enable policy-makers and stakeholders to select and implement the most appropriate strategies, measures, and cost-effective approaches to reduce casualties of all road user types and all severities. This document is the second deliverable (4.2) of work package 4, which is dedicated to identifying and assessing road safety measures related to road users in terms of their effectiveness. The focus of deliverable 4.2 is on the identification and assessment of countermeasures and describes the corresponding operational procedure and outcomes. Measures which intend to increase road safety of all kind of road user groups have been considered [...continues]