Mechanisms of Cognitive Impairment in Cerebral Small Vessel Disease: Multimodal MRI Results from the St George's Cognition and Neuroimaging in Stroke (SCANS) Study.

Cerebral small vessel disease (SVD) is a common cause of vascular cognitive impairment. A number of disease features can be assessed on MRI including lacunar infarcts, T2 lesion volume, brain atrophy, and cerebral microbleeds. In addition, diffusion tensor imaging (DTI) is sensitive to disruption of white matter ultrastructure, and recently it has been suggested that additional information on the pattern of damage may be obtained from axial diffusivity, a proposed marker of axonal damage, and radial diffusivity, an indicator of demyelination. We determined the contribution of these whole brain MRI markers to cognitive impairment in SVD. Consecutive patients with lacunar stroke and confluent leukoaraiosis were recruited into the ongoing SCANS study of cognitive impairment in SVD (n = 115), and underwent neuropsychological assessment and multimodal MRI. SVD subjects displayed poor performance on tests of executive function and processing speed. In the SVD group brain volume was lower, white matter hyperintensity volume higher and all diffusion characteristics differed significantly from control subjects (n = 50). On multi-predictor analysis independent predictors of executive function in SVD were lacunar infarct count and diffusivity of normal appearing white matter on DTI. Independent predictors of processing speed were lacunar infarct count and brain atrophy. Radial diffusivity was a stronger DTI predictor than axial diffusivity, suggesting ischaemic demyelination, seen neuropathologically in SVD, may be an important predictor of cognitive impairment in SVD. Our study provides information on the mechanism of cognitive impairment in SVD

Cooperative coupling of ultracold atoms and surface plasmons

Cooperative coupling between optical emitters and light fields is one of the outstanding goals in quantum technology. It is both fundamentally interesting for the extraordinary radiation properties of the participating emitters and has many potential applications in photonics. While this goal has been achieved using high-finesse optical cavities, cavity-free approaches that are broadband and easy to build have attracted much attention recently. Here we demonstrate cooperative coupling of ultracold atoms with surface plasmons propagating on a plane gold surface. While the atoms are moving towards the surface they are excited by an external laser pulse. Excited surface plasmons are detected via leakage radiation into the substrate of the gold layer. A maximum Purcell factor of $\eta_\mathrm{P}=4.9$ is reached at an optimum distance of $z=250~\mathrm{nm}$ from the surface. The coupling leads to the observation of a Fano-like resonance in the spectrum.Comment: 9 pages, 4 figure

Live Imaging at the Onset of Cortical Neurogenesis Reveals Differential Appearance of the Neuronal Phenotype in Apical versus Basal Progenitor Progeny

The neurons of the mammalian brain are generated by progenitors dividing either at the apical surface of the ventricular zone (neuroepithelial and radial glial cells, collectively referred to as apical progenitors) or at its basal side (basal progenitors, also called intermediate progenitors). For apical progenitors, the orientation of the cleavage plane relative to their apical-basal axis is thought to be of critical importance for the fate of the daughter cells. For basal progenitors, the relationship between cell polarity, cleavage plane orientation and the fate of daughter cells is unknown. Here, we have investigated these issues at the very onset of cortical neurogenesis. To directly observe the generation of neurons from apical and basal progenitors, we established a novel transgenic mouse line in which membrane GFP is expressed from the beta-III-tubulin promoter, an early pan-neuronal marker, and crossed this line with a previously described knock-in line in which nuclear GFP is expressed from the Tis21 promoter, a pan-neurogenic progenitor marker. Mitotic Tis21-positive basal progenitors nearly always divided symmetrically, generating two neurons, but, in contrast to symmetrically dividing apical progenitors, lacked apical-basal polarity and showed a nearly randomized cleavage plane orientation. Moreover, the appearance of beta-III-tubulin–driven GFP fluorescence in basal progenitor-derived neurons, in contrast to that in apical progenitor-derived neurons, was so rapid that it suggested the initiation of the neuronal phenotype already in the progenitor. Our observations imply that (i) the loss of apical-basal polarity restricts neuronal progenitors to the symmetric mode of cell division, and that (ii) basal progenitors initiate the expression of neuronal phenotype already before mitosis, in contrast to apical progenitors

Asymptotic Expansions for Stationary Distributions of Perturbed Semi-Markov Processes

New algorithms for computing of asymptotic expansions for stationary distributions of nonlinearly perturbed semi-Markov processes are presented. The algorithms are based on special techniques of sequential phase space reduction, which can be applied to processes with asymptotically coupled and uncoupled finite phase spaces.Comment: 83 page

Full genome comparison and characterization of avian H10 viruses with different pathogenicity in Mink (Mustela vison) reveals genetic and functional differences in the non-structural gene

<p>Abstract</p> <p>Background</p> <p>The unique property of some avian H10 viruses, particularly the ability to cause severe disease in mink without prior adaptation, enabled our study. Coupled with previous experimental data and genetic characterization here we tried to investigate the possible influence of different genes on the virulence of these H10 avian influenza viruses in mink.</p> <p>Results</p> <p>Phylogenetic analysis revealed a close relationship between the viruses studied. Our study also showed that there are no genetic differences in receptor specificity or the cleavability of the haemagglutinin proteins of these viruses regardless of whether they are of low or high pathogenicity in mink.</p> <p>In poly I:C stimulated mink lung cells the NS1 protein of influenza A virus showing high pathogenicity in mink down regulated the type I interferon promoter activity to a greater extent than the NS1 protein of the virus showing low pathogenicity in mink.</p> <p>Conclusions</p> <p>Differences in pathogenicity and virulence in mink between these strains could be related to clear amino acid differences in the non structural 1 (NS1) protein. The NS gene of mink/84 appears to have contributed to the virulence of the virus in mink by helping the virus evade the innate immune responses.</p

Swedish social insurance officers' experiences of difficulties in assessing applications for disability pensions – an interview study

<p>Abstract</p> <p>Background</p> <p>In this study the focus is on social insurance officers judging applications for disability pensions. The number of applications for disability pension increased during the late 1990s, which has resulted in an increasing number of disability pensions in Sweden. A more restrictive attitude towards the clients has however evolved, as societal costs have increased and governmental guidelines now focus on reducing costs. As a consequence, the quantitative and qualitative demands on social insurance officers when handling applications for disability pensions may have increased. The aim of this study was therefore to describe the social insurance officers' experiences of assessing applications for disability pensions after the government's introduction of stricter regulations.</p> <p>Methods</p> <p>Qualitative methodology was employed and a total of ten social insurance officers representing different experiences and ages were chosen. Open-ended interviews were performed with the ten social insurance officers. Data was analysed with inductive content analysis.</p> <p>Results</p> <p>Three themes could be identified as problematic in the social insurance officers' descriptions of dealing with the applications in order to reach a decision on whether the issue qualified applicants for a disability pension or not: 1. Clients are heterogeneous. 2. Ineffective and time consuming waiting for medical certificates impede the decision process. 3. Perspectives on the issue of work capacity differed among different stakeholders. The backgrounds of the clients differ considerably, leading to variation in the quality and content of applications. Social insurance officers had to make rapid decisions within a limited time frame, based on limited information, mainly on the basis of medical certificates that were often insufficient to judge work capacity. The role as coordinating actor with other stakeholders in the welfare system was perceived as frustrating, since different stakeholders have different goals and demands. The social insurance officers experience lack of control over the decision process, as regulations and other stakeholders restrict their work.</p> <p>Conclusion</p> <p>A picture emerges of difficulties due to disharmonized systems, stakeholder-bound goals causing some clients to fall between two stools, or leading to unnecessary waiting times, which may limit the clients' ability to take an active part in a constructive process. Increased communication with physicians about how to elaborate the medical certificates might improve the quality of certificates and thereby reduce the clients waiting time.</p

Chromosome 7 and 19 Trisomy in Cultured Human Neural Progenitor Cells

BACKGROUND:Stem cell expansion and differentiation is the foundation of emerging cell therapy technologies. The potential applications of human neural progenitor cells (hNPCs) are wide ranging, but a normal cytogenetic profile is important to avoid the risk of tumor formation in clinical trials. FDA approved clinical trials are being planned and conducted for hNPC transplantation into the brain or spinal cord for various neurodegenerative disorders. Although human embryonic stem cells (hESCs) are known to show recurrent chromosomal abnormalities involving 12 and 17, no studies have revealed chromosomal abnormalities in cultured hNPCs. Therefore, we investigated frequently occurring chromosomal abnormalities in 21 independent fetal-derived hNPC lines and the possible mechanisms triggering such aberrations. METHODS AND FINDINGS:While most hNPC lines were karyotypically normal, G-band karyotyping and fluorescent in situ hybridization (FISH) analyses revealed the emergence of trisomy 7 (hNPC(+7)) and trisomy 19 (hNPC(+19)), in 24% and 5% of the lines, respectively. Once detected, subsequent passaging revealed emerging dominance of trisomy hNPCs. DNA microarray and immunoblotting analyses demonstrate epidermal growth factor receptor (EGFR) overexpression in hNPC(+7) and hNPC(+19) cells. We observed greater levels of telomerase (hTERT), increased proliferation (Ki67), survival (TUNEL), and neurogenesis (beta(III)-tubulin) in hNPC(+7) and hNPC(+19), using respective immunocytochemical markers. However, the trisomy lines underwent replicative senescence after 50-60 population doublings and never showed neoplastic changes. Although hNPC(+7) and hNPC(+19) survived better after xenotransplantation into the rat striatum, they did not form malignant tumors. Finally, EGF deprivation triggered a selection of trisomy 7 cells in a diploid hNPC line. CONCLUSIONS:We report that hNPCs are susceptible to accumulation of chromosome 7 and 19 trisomy in long-term cell culture. These results suggest that micro-environmental cues are powerful factors in the selection of specific hNPC aneuploidies, with trisomy of chromosome 7 being the most common. Given that a number of stem cell based clinical trials are being conducted or planned in USA and a recent report in PLoS Medicine showing the dangers of grafting an inordinate number of cells, these data substantiate the need for careful cytogenetic evaluation of hNPCs (fetal or hESC-derived) before their use in clinical or basic science applications

A multidisciplinary, multifactorial intervention program reduces postoperative falls and injuries after femoral neck fracture

INTRODUCTION: This study evaluates whether a postoperative multidisciplinary, intervention program, including systematic assessment and treatment of fall risk factors, active prevention, detection, and treatment of postoperative complications, could reduce inpatient falls and fall-related injuries after a femoral neck fracture. METHODS: A randomized, controlled trial at the orthopedic and geriatric departments at Umeå University Hospital, Sweden, included 199 patients with femoral neck fracture, aged  ≥70 years. RESULTS: Twelve patients fell 18 times in the intervention group compared with 26 patients suffering 60 falls in the control group. Only one patient with dementia fell in the intervention group compared with 11 in the control group. The crude postoperative fall incidence rate was 6.29/1,000 days in the intervention group vs 16.28/1,000 days in the control group. The incidence rate ratio was 0.38 [95% confidence interval (CI): 0.20 – 0.76, p = 0.006] for the total sample and 0.07 (95% CI: 0.01–0.57, p=0.013) among patients with dementia. There were no new fractures in the intervention group but four in the control group. CONCLUSION: A team applying comprehensive geriatric assessment and rehabilitation, including prevention, detection, and treatment of fall risk factors, can successfully prevent inpatient falls and injuries, even in patients with dementia