94 research outputs found
Survey of the Status of Small Armed and Unarmed Uninhabited Aircraft
The project ‘Preventive Arms Control for Small and Very Small Armed Aircraft and Missiles’
investigates the properties of ever smaller aircraft and missiles. This project report no. 1 covers
the status of aircraft worldwide, including relevant unarmed vehicles but excluding hobby aircraft.
Small and very small aircraft are defined by size: below 2 m and below 0.2 m, respectively. After an
elementary introduction into aerodynamics a technical overview is given, looking at airframe
configurations, materials and manufacturing, power and propulsion, guidance, launch and recovery,
and payloads. Future possibilities and trends are illustrated by presenting military research and
development of the technological leader, the USA. Short chapters deal with swarms and with
countermeasures. The worldwide survey has resulted in a database that contains 129 types from 27
countries. The publicly available properties are given in 26 categories. Statistical evaluations
cover several key parameters
East Mediterr Health J
Background: The emergence and re-emergence of viral haemorrhagic fevers (VHFs) is a growing concern worldwide. They are associated with major epidemics with an estimated 51-101 million cases each year, of which around 67 000 are fatal. In 2007, 13 countries in the Eastern Mediterranean Region reported VHF cases. Aims: The main purpose of the study was to review the epidemiological situation in the Region vis-a-vis VHFs to obtain baseline epidemiological information for the establishment of the Emerging Dangerous Pathogen Laboratory Network (EDPLN). Methods: A literature search was performed using PubMed, ProMED-Mail and GIDEON databases. Reported data included disease burden (reported cases and deaths), human prevalence (general population, high-risk groups), vectors and reservoirs. A scoring method was employed to divide countries into 4 groups (very highly, highly, medium and low affected countries). Results: Very highly affected countries were Afghanistan, Egypt, Islamic Republic of Iran, Saudi Arabia and Sudan. Highly affected countries were Djibouti, Morocco, Oman, Pakistan, Tunisia and Yemen. Medium affected countries were Iraq, Somalia and United Arab Emirates. Low affected countries were Bahrain, Jordan, Lebanon, Libya, Palestine, Qatar and Syrian Arab Republic. Conclusions: This study contributes in prioritizing countries to be part of EDPLN and in addressing specific needs related to outbreak investigations, surveillance and research
Timeliness of Surveillance during Outbreak of Shiga Toxin–producing Escherichia coli Infection, Germany, 2011
In the context of a large outbreak of Shiga toxin–producing Escherichia coli O104:H4 in Germany, we quantified the timeliness of the German surveillance system for hemolytic uremic syndrome and Shiga toxin–producing E. coli notifiable diseases during 2003–2011. Although reporting occurred faster than required by law, potential for improvement exists at all levels of the information chain
Everolimus in Combination with Cyclosporin A as Pre- and Posttransplantation Immunosuppressive Therapy in Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Everolimus (RAD001) is an mTOR inhibitor that has been successfully used as an immunosuppressant in solid-organ transplantation. Data in allogeneic hematopoietic stem cell transplantation (HSCT) is limited. This study aimed to investigate pharmacokinetics, safety, and efficacy of RAD001 in a canine allogeneic HSCT model. First, pharmacokinetics of RAD001 were performed in healthy dogs in order to determine the appropriate dosing. Doses of 0.25 mg RAD001 twice daily in combination with 15 mg/kg cyclosporin A (CsA) twice daily were identified as appropriate starting doses to achieve the targeted range of RAD001 (3-8 μg/L) when orally administered. Subsequently, 10 dogs were transplanted using 2 Gy total body irradiation (TBI) for conditioning and 0.25 mg RAD001 twice daily plus 15 mg/kg CsA twice daily for pre- and posttransplantation immunosuppression. Seven of the 10 transplanted dogs were maintained at the starting RAD001 dose throughout the study. For the remaining 3 dogs, dose adjustments were necessary. RAD001 accumulation over time did not occur. All dogs initially engrafted. Five dogs eventually rejected the graft (weeks 10, 10, 13, 27, and 56). Two dogs died of pneumonia (weeks 8 and 72) but were chimeric until then. Total cholesterol rose from median 4.1 mmol/L (3.5-5.7 mmol/L) before HSCT to 6.0 mmol/l (5.0-8.5 mmol/l) at day 21 after HSCT, but remained always within normal range. Changes in creatinine and triglyceride values were not observed. Long-term engraftment rates were inferior to sirolimus/CsA and mycophenolate mofetil (MMF)/CsA regimen, respectively. RAD001/CsA caused a more pronounced reduction of platelet counts to median 2 × 109/L (range: 0-21 × 109/L) and longer time to platelet recovery of 21 days (range: 14-24 days) compared with MMF/CsA. CsA c2h levels were significantly enhanced in the RAD001/CsA regimen, but c0h and area under the curve from 0 to 12 hours (AUC0-12h) values did not differ compared with an MMF/CsA immunosuppression. In summary, immunosuppression consisting of RAD001 and CsA is well tolerated but not as efficient as with other established immunosuppressants in a canine nonmyeloablative HSCT regimen. Hence, our study does not support the application of RAD001/CsA as standard practice in this setting
Severe Cases of Pandemic (H1N1) 2009 in Children, Germany
In a hospital-based observational study in Germany, we investigated children admitted to pediatric intensive care units and deaths caused by confirmed pandemic (H1N1) 2009 to identify risk factors and outcomes in critically ill children. Ninety-three children were eligible for our study, including 9 with hospital-acquired infections. Seventy-five percent had underlying chronic medical conditions; neurodevelopmental disorders were most prevalent (57%). The proportion of patients having >1 risk factor increased with age in years (odds ratio 1.21, p = 0.007). Of 15 deaths, 11 occurred in a pediatric intensive care unit (case-fatality rate 12%, 95% confidence interval 6%–21%). Only 9% of the children had been vaccinated against pandemic (H1N1) 2009; all survived. Our results stress the role of underlying risk factors, especially neurodevelopmental disorders, and the need for improving preventive measures to reduce severe disease and adverse outcomes of pandemic (H1N1) 2009 in children
Trials
After publication of the original article [1], the authors have notified us of an additional acknowledgement they wish to bring for their paper
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The item versus the object in memory: on the implausibility of overwriting as a mechanism for forgetting in short-term memory
The nature of forgetting in short-term memory remains a disputed topic, with much debate focussed upon whether decay plays a fundamental role (Berman et al., 2009; Altmann and Schunn, 2012; Barrouillet et al., 2012; Neath and Brown, 2012; Oberauer and Lewandowsky, 2013; Ricker et al., 2014) but much less focus on other plausible mechanisms. One such mechanism of long-standing in auditory memory is overwriting (e.g., Crowder and Morton, 1969) in which some aspects of a representation are “overwritten” and rendered inaccessible by the subsequent presentation of a further item. Here, we review the evidence for different forms of overwriting (at the feature and item levels) and examine the plausibility of this mechanism both as a form of auditory memory and when viewed in the context of a larger hearing, speech and language understanding system
The Rare IL22RA2 Signal Peptide Coding Variant rs28385692 Decreases Secretion of IL-22BP Isoform-1, -2 and -3 and Is Associated with Risk for Multiple Sclerosis.
The IL22RA2 locus is associated with risk for multiple sclerosis (MS) but causative variants are yet to be determined. In a single nucleotide polymorphism (SNP) screen of this locus in a Basque population, rs28385692, a rare coding variant substituting Leu for Pro at position 16 emerged significantly (p = 0.02). This variant is located in the signal peptide (SP) shared by the three secreted protein isoforms produced by IL22RA2 (IL-22 binding protein-1(IL-22BPi1), IL-22BPi2 and IL-22BPi3). Genotyping was extended to a Europe-wide case-control dataset and yielded high significance in the full dataset (p = 3.17 × 10-4). Importantly, logistic regression analyses conditioning on the main known MS-associated SNP at this locus, rs17066096, revealed that this association was independent from the primary association signal in the full case-control dataset. In silico analysis predicted both disruption of the alpha helix of the H-region of the SP and decreased hydrophobicity of this region, ultimately affecting the SP cleavage site. We tested the effect of the p.Leu16Pro variant on the secretion of IL-22BPi1, IL-22BPi2 and IL-22BPi3 and observed that the Pro16 risk allele significantly lowers secretion levels of each of the isoforms to around 50%-60% in comparison to the Leu16 reference allele. Thus, our study suggests that genetically coded decreased levels of IL-22BP isoforms are associated with augmented risk for MS
Unique Microbial Catabolic Pathway for the Human Core N-Glycan Constituent Fucosyl-α-1,6-N-Acetylglucosamine-Asparagine
The survival of commensal bacteria in the human gut partially depends on their ability to metabolize host-derived molecules. The use of the glycosidic moiety of N-glycoproteins by bacteria has been reported, but the role of N-glycopeptides or glycoamino acids as the substrates for bacterial growth has not been evaluated. We have identified in Lactobacillus casei strain BL23 a gene cluster (alf-2) involved in the catabolism of the glycoamino acid fucosyl-α-1,6-N-GlcNAc-Asn (6'FN-Asn), a constituent of the core-fucosylated structures of mammalian N-glycoproteins. The cluster consists of the genes alfHC, encoding a major facilitator superfamily (MFS) permease and the α-L-fucosidase AlfC, and the divergently oriented asdA (aspartate 4-decarboxylase), alfR2 (transcriptional regulator), pepV (peptidase), asnA2 (glycosyl-asparaginase), and sugK (sugar kinase) genes. Knockout mutants showed that alfH, alfC, asdA, asnA2, and sugK are necessary for efficient 6'FN-Asn utilization. The alf-2 genes are induced by 6'FN-Asn, but not by its glycan moiety, via the AlfR2 regulator. The constitutive expression of alf-2 genes in an alfR2 strain allowed the metabolism of a variety of 6'-fucosyl-glycans. However, GlcNAc-Asn did not support growth in this mutant background, indicating that the presence of a 6'-fucose moiety is crucial for substrate transport via AlfH. Within bacteria, 6'FN-Asn is defucosylated by AlfC, generating GlcNAc-Asn. This glycoamino acid is processed by the glycosylasparaginase AsnA2. GlcNAc-Asn hydrolysis generates aspartate and GlcNAc, which is used as a fermentable source by L. casei These data establish the existence in a commensal bacterial species of an exclusive metabolic pathway likely to scavenge human milk and mucosal fucosylated N-glycopeptides in the gastrointestinal tract. IMPORTANCE The gastrointestinal tract accommodates more than 1014 microorganisms that have an enormous impact on human health. The mechanisms enabling commensal bacteria and administered probiotics to colonize the gut remain largely unknown. The ability to utilize host-derived carbon and energy resources available at the mucosal surfaces may provide these bacteria with a competitive advantage in the gut. Here, we have identified in the commensal species Lactobacillus casei a novel metabolic pathway for the utilization of the glycoamino acid fucosyl-α-1,6-N-GlcNAc-Asn, which is present in the core-fucosylated N-glycoproteins from mammalians. These results give insight into the molecular interactions between the host and commensal/probiotic bacteria and may help to devise new strategies to restore gut microbiota homeostasis in diseases associated with dysbiotic microbiota
Unchanged Severity of Influenza A(H1N1)pdm09 Infection in Children during First Postpandemic Season
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