Setting up a Common European Asylum System : Report on the application of existing instruments and proposals for the new system

The study assesses firstly the evaluation process of the first generation of asylum instruments while underlining the possibilities to improve it. It analyses secondly the asylum "acquis" regarding distribution of refugees between Member States, the eligibility for protection, the status of protected persons regarding detention and vulnerability, asylum procedures and the external dimension by formulating short-term recommendations of each area. Its last part is devoted to the long term evolution of the Common European Asylum System regarding the legal context including the accession of the EU to the Geneva Convention, the institutional perspectives including the new European Support Office, the jurisdictional perspective, the substantive perspective, the distributive perspective and the external perspective

Biofilm associated genotypes of multiple antibiotic resistant Pseudomonas aeruginosa

Background: Pseudomonas aeruginosa is a ubiquitous environmental microorganism and also a common cause of infection. Its ability to survive in many different environments and persistently colonize humans is linked to its presence in biofilms formed on indwelling device surfaces. Biofilm promotes adhesion to, and survival on surfaces, protects from desiccation and the actions of antibiotics and disinfectants. Results: We examined the genetic basis for biofilm production on polystyrene at room (22 °C) and body temperature (37 °C) within 280 P. aeruginosa. 193 isolates (69 %) produced more biofilm at 22 °C than at 37 °C. Using GWAS and pan-GWAS, we found a number of accessory genes significantly associated with greater biofilm production at 22 °C. Many of these are present on a 165 kb region containing genes for heavy metal resistance (arsenic, copper, mercury and cadmium), transcriptional regulators and methytransferases. We also discovered multiple core genome SNPs in the A-type flagellin gene and Type II secretion system gene xpsD. Analysis of biofilm production of isolates of the MDR ST111 and ST235 lineages on stainless-steel revealed several accessory genes associated with enhanced biofilm production. These include a putative translocase with homology to a Helicobacter pylori type IV secretion system protein, a TA system II toxin gene and the alginate biosynthesis gene algA, several transcriptional regulators and methytransferases as well as core SNPs in genes involved in quorum sensing and protein translocation. Conclusions: Using genetic association approaches we discovered a number of accessory genes and core-genome SNPs that were associated with enhanced early biofilm formation at 22 °C compared to 37 °C. These included a 165 kb genomic island containing multiple heavy metal resistance genes, transcriptional regulators and methyltransferases. We hypothesize that this genomic island may be associated with overall genotypes that are environmentally adapted to survive at lower temperatures. Further work to examine their importance in, for example gene-knockout studies, are required to confirm their relevance. GWAS and pan-GWAS approaches have great potential as a first step in examining the genetic basis of novel bacterial phenotypes

PRIMA subretinal wireless photovoltaic microchip implantation in non-human primate and feline models

PURPOSE: To evaluate the surgical technique for subretinal implantation of two sizes of PRIMA photovoltaic wireless microchip in two animal models, and refine these surgical procedures for human trials. METHODS: Cats and Macaca fascicularis primates with healthy retina underwent vitrectomy surgery and were implanted with subretinal wireless photovoltaic microchip at the macula/central retina. The 1.5mm PRIMA chip was initially studied in feline eyes. PRIMA implant (2mm,1.5mm sizes) arrays were studied in primates. Feasibility of subretinal chip implantation was evaluated with a newly-developed surgical technique, with surgical complications and adverse events recorded. RESULTS: The 1.5mm implant was placed in the central retina of 11 feline eyes, with implantation duration 43-106 days. The 1.5mm implant was correctly positioned into central macula of 11 primate eyes, with follow-up periods of minimum 6 weeks (n = 11), 2 years (n = 2), and one eye for 3 years. One primate eye underwent multi-chip 1.5mm implantation using two 1.5mm chips. The 2mm implant was delivered to 4 primate eyes. Optical coherence tomography confirmed correct surgical placement of photovoltaic arrays in the subretinal space in all 26 eyes. Intraoperative complications in primate eyes included retinal tear, macular hole, retinal detachment, and vitreous hemorrhage that resolved spontaneously. Postoperatively, there was no case of significant ocular inflammation in the 1.5mm implant group. CONCLUSIONS: We report subretinal implantation of 1.5mm and 2mm photovoltaic arrays in the central retina of feline and central macula of primate eyes with a low rate of device-related complications. The in vivo PRIMA implantation technique has been developed and refined for use for a 2mm PRIMA implant in ongoing human trials

PRIMA subretinal wireless photovoltaic microchip implantation in non-human primate and feline models

Purpose To evaluate the surgical technique for subretinal implantation of two sizes of PRIMA photovoltaic wireless microchip in two animal models, and refine these surgical procedures for human trials. Methods Cats and Macaca fascicularis primates with healthy retina underwent vitrectomy surgery and were implanted with subretinal wireless photovoltaic microchip at the macula/central retina. The 1.5mm PRIMA chip was initially studied in feline eyes. PRIMA implant (2mm,1.5mm sizes) arrays were studied in primates. Feasibility of subretinal chip implantation was evaluated with a newly-developed surgical technique, with surgical complications and adverse events recorded. Results The 1.5mm implant was placed in the central retina of 11 feline eyes, with implantation duration 43-106 days. The 1.5mm implant was correctly positioned into central macula of 11 primate eyes, with follow-up periods of minimum 6 weeks (n = 11), 2 years (n = 2), and one eye for 3 years. One primate eye underwent multi-chip 1.5mm implantation using two 1.5mm chips. The 2mm implant was delivered to 4 primate eyes. Optical coherence tomography confirmed correct surgical placement of photovoltaic arrays in the subretinal space in all 26 eyes. Intraoperative complications in primate eyes included retinal tear, macular hole, retinal detachment, and vitreous hemorrhage that resolved spontaneously. Postoperatively, there was no case of significant ocular inflammation in the 1.5mm implant group. Conclusions We report subretinal implantation of 1.5mm and 2mm photovoltaic arrays in the central retina of feline and central macula of primate eyes with a low rate of device-related complications. The in vivo PRIMA implantation technique has been developed and refined for use for a 2mm PRIMA implant in ongoing human trials

Emergence of Epidemic Neisseria meningitidis Serogroup X Meningitis in Togo and Burkina Faso

Serogroup X meningococci (NmX) historically have caused sporadic and clustered meningitis cases in sub-Saharan Africa. To study recent NmX epidemiology, we analyzed data from population-based, sentinel and passive surveillance, and outbreak investigations of bacterial meningitis in Togo and Burkina Faso during 2006–2010. Cerebrospinal fluid specimens were analyzed by PCR. In Togo during 2006–2009, NmX accounted for 16% of the 702 confirmed bacterial meningitis cases. Kozah district experienced an NmX outbreak in March 2007 with an NmX seasonal cumulative incidence of 33/100,000. In Burkina Faso during 2007–2010, NmX accounted for 7% of the 778 confirmed bacterial meningitis cases, with an increase from 2009 to 2010 (4% to 35% of all confirmed cases, respectively). In 2010, NmX epidemics occurred in northern and central regions of Burkina Faso; the highest district cumulative incidence of NmX was estimated as 130/100,000 during March–April. Although limited to a few districts, we have documented NmX meningitis epidemics occurring with a seasonal incidence previously only reported in the meningitis belt for NmW135 and NmA, which argues for development of an NmX vaccine

The longitudinal changes of BOLD response and cerebral hemodynamics from acute to subacute stroke. A fMRI and TCD study

<p>Abstract</p> <p>Background</p> <p>By mapping the dynamics of brain reorganization, functional magnetic resonance imaging MRI (fMRI) has allowed for significant progress in understanding cerebral plasticity phenomena after a stroke. However, cerebro-vascular diseases can affect blood oxygen level dependent (BOLD) signal. Cerebral autoregulation is a primary function of cerebral hemodynamics, which allows to maintain a relatively constant blood flow despite changes in arterial blood pressure and perfusion pressure. Cerebral autoregulation is reported to become less effective in the early phases post-stroke.</p> <p>This study investigated whether any impairment of cerebral hemodynamics that occurs during the acute and the subacute phases of ischemic stroke is related to changes in BOLD response.</p> <p>We enrolled six aphasic patients affected by acute stroke. All patients underwent a Transcranial Doppler to assess cerebral autoregulation (Mx index) and fMRI to evaluate the amplitude and the peak latency (time to peak-TTP) of BOLD response in the acute (i.e., within four days of stroke occurrence) and the subacute (i.e., between five and twelve days after stroke onset) stroke phases.</p> <p>Results</p> <p>As patients advanced from the acute to subacute stroke phase, the affected hemisphere presented a BOLD TTP increase (p = 0.04) and a deterioration of cerebral autoregulation (Mx index increase, p = 0.046). A similar but not significant trend was observed also in the unaffected hemisphere. When the two hemispheres were grouped together, BOLD TTP delay was significantly related to worsening cerebral autoregulation (Mx index increase) (Spearman's rho = 0.734; p = 0.01).</p> <p>Conclusions</p> <p>The hemodynamic response function subtending BOLD signal may present a delay in peak latency that arises as patients advance from the acute to the subacute stroke phase. This delay is related to the deterioration of cerebral hemodynamics. These findings suggest that remodeling the fMRI hemodynamic response function in the different phases of stroke may optimize the detection of BOLD signal changes.</p

Correlation between phenotypic antibiotic susceptibility and the resistome in Pseudomonas aeruginosa

Genetic determinants of antibiotic resistance (AR) have been extensively investigated. High-throughput sequencing allows for the assessment of the relationship between genotype and phenotype. A panel of 672 Pseudomonas aeruginosa strains was analysed, including representatives of globally disseminated multidrug-resistant and extensively drug-resistant clones; genomes and multiple antibiograms were available. This panel was annotated for AR gene presence and polymorphism, defining a resistome in which integrons were included. Integrons were present in >70 distinct cassettes, with In5 being the most prevalent. Some cassettes closely associated with clonal complexes, whereas others spread across the phylogenetic diversity, highlighting the importance of horizontal transfer. A resistome-wide association study (RWAS) was performed for clinically relevant antibiotics by correlating the variability in minimum inhibitory concentration (MIC) values with resistome data. Resistome annotation identified 147 loci associated with AR. These loci consisted mainly of acquired genomic elements and intrinsic genes. The RWAS allowed for correct identification of resistance mechanisms for meropenem, amikacin, levofloxacin and cefepime, and added 46 novel mutations. Among these, 29 were variants of the oprD gene associated with variation in meropenem MIC. Using genomic and MIC data, phenotypic AR was successfully correlated with molecular determinants at the whole-genome sequence level

The Human Proteins MBD5 and MBD6 Associate with Heterochromatin but They Do Not Bind Methylated DNA

BACKGROUND: MBD5 and MBD6 are two uncharacterized mammalian proteins that contain a putative Methyl-Binding Domain (MBD). In the proteins MBD1, MBD2, MBD4, and MeCP2, this domain allows the specific recognition of DNA containing methylated cytosine; as a consequence, the proteins serve as interpreters of DNA methylation, an essential epigenetic mark. It is unknown whether MBD5 or MBD6 also bind methylated DNA; this question has interest for basic research, but also practical consequences for human health, as MBD5 deletions are the likely cause of certain cases of mental retardation. PRINCIPAL FINDINGS: Here we report the first functional characterization of MBD5 and MBD6. We have observed that the proteins colocalize with heterochromatin in cultured cells, and that this localization requires the integrity of their MBD. However, heterochromatic localization is maintained in cells with severely decreased levels of DNA methylation. In vitro, neither MBD5 nor MBD6 binds any of the methylated sequences DNA that were tested. CONCLUSIONS: Our data suggest that MBD5 and MBD6 are unlikely to be methyl-binding proteins, yet they may contribute to the formation or function of heterochromatin. One isoform of MBD5 is highly expressed in oocytes, which suggests a possible role in epigenetic reprogramming after fertilization