An observational study of patient characteristics associated with the mode of admission to acute stroke services in North East, England

Objective Effective provision of urgent stroke care relies upon admission to hospital by emergency ambulance and may involve pre-hospital redirection. The proportion and characteristics of patients who do not arrive by emergency ambulance and their impact on service efficiency is unclear. To assist in the planning of regional stroke services we examined the volume, characteristics and prognosis of patients according to the mode of presentation to local services. Study design and setting A prospective regional database of consecutive acute stroke admissions was conducted in North East, England between 01/09/10-30/09/11. Case ascertainment and transport mode were checked against hospital coding and ambulance dispatch databases. Results Twelve acute stroke units contributed data for a mean of 10.7 months. 2792/3131 (89%) patients received a diagnosis of stroke within 24 hours of admission: 2002 arrivals by emergency ambulance; 538 by private transport or non-emergency ambulance; 252 unknown mode. Emergency ambulance patients were older (76 vs 69 years), more likely to be from institutional care (10% vs 1%) and experiencing total anterior circulation symptoms (27% vs 6%). Thrombolysis treatment was commoner following emergency admission (11% vs 4%). However patients attending without emergency ambulance had lower inpatient mortality (2% vs 18%), a lower rate of institutionalisation (1% vs 6%) and less need for daily carers (7% vs 16%). 149/155 (96%) of highly dependent patients were admitted by emergency ambulance, but none received thrombolysis. Conclusion Presentations of new stroke without emergency ambulance involvement were not unusual but were associated with a better outcome due to younger age, milder neurological impairment and lower levels of pre-stroke dependency. Most patients with a high level of pre-stroke dependency arrived by emergency ambulance but did not receive thrombolysis. It is important to be aware of easily identifiable demographic groups that differ in their potential to gain from different service configurations

Symptomatic hemorrhage after alteplase therapy not due to silent ischemia

BACKGROUND: Stroke thrombolysis-related intracerebral hemorrhage may occur remotely from the anatomical site of ischemia. One postulated mechanism for this is simultaneous multiple embolization with hemorrhage into a "silent" area of ischemia. RESULTS: A patient suffered a disabling stroke affecting the right cerebral hemisphere. He was treated with intravenous alteplase and underwent extensive early imaging with multimodal MRI. Several hours after treatment he developed a brainstem hemorrhage despite having no evidence of ischemia on DWI MRI in the brainstem. CONCLUSION: Not all occurrences of remote ICH after stroke thrombolysis are secondary to multiple emboli with silent ischemia

Ghosts of Yellowstone: Multi-Decadal Histories of Wildlife Populations Captured by Bones on a Modern Landscape

Natural accumulations of skeletal material (death assemblages) have the potential to provide historical data on species diversity and population structure for regions lacking decades of wildlife monitoring, thereby contributing valuable baseline data for conservation and management strategies. Previous studies of the ecological and temporal resolutions of death assemblages from terrestrial large-mammal communities, however, have largely focused on broad patterns of community composition in tropical settings. Here, I expand the environmental sampling of large-mammal death assemblages into a temperate biome and explore more demanding assessments of ecological fidelity by testing their capacity to record past population fluctuations of individual species in the well-studied ungulate community of Yellowstone National Park (Yellowstone). Despite dramatic ecological changes following the 1988 wildfires and 1995 wolf re-introduction, the Yellowstone death assemblage is highly faithful to the living community in species richness and community structure. These results agree with studies of tropical death assemblages and establish the broad capability of vertebrate remains to provide high-quality ecological data from disparate ecosystems and biomes. Importantly, the Yellowstone death assemblage also correctly identifies species that changed significantly in abundance over the last 20 to ∼80 years and the directions of those shifts (including local invasions and extinctions). The relative frequency of fresh versus weathered bones for individual species is also consistent with documented trends in living population sizes. Radiocarbon dating verifies the historical source of bones from Equus caballus (horse): a functionally extinct species. Bone surveys are a broadly valuable tool for obtaining population trends and baseline shifts over decadal-to-centennial timescales

New MR sequences in daily practice: susceptibility weighted imaging. A pictorial essay

Background Susceptibility-weighted imaging (SWI) is a relatively new magnetic resonance (MR) technique that exploits the magnetic susceptibility differences of various tissues, such as blood, iron and calcification, as a new source of contrast enhancement. This pictorial review is aimed at illustrating and discussing its main clinical applications. Methods SWI is based on high-resolution, threedimensional (3D), fully velocity-compensated gradientecho sequences using both magnitude and phase images. A phase mask obtained from the MR phase images is multiplied with magnitude images in order to increase the visualisation of the smaller veins and other sources of susceptibility effects, which are displayed at best after postprocessing of the 3D dataset with the minimal intensity projection (minIP) algorithm. Results SWI is very useful in detecting cerebral microbleeds in ageing and occult low-flow vascular malformations, in characterising brain tumours and degenerative diseases of the brain, and in recognizing calcifications in various pathological conditions. The phase images are especially useful in differentiating between paramagnetic susceptibility effects of blood and diamagnetic effects of calcium. SWI can also be used to evaluate changes in iron content in different neurodegenerative disorders. Conclusion SWI is useful in differentiating and characterising diverse brain disorders

Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome

Transposable elements (TEs) have no longer been totally considered as “junk DNA” for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Technologies based on 3C(chromosomeconformation capture) have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions (hESC: r=0.9, P<2.2×1016; IMR90 fibroblasts: r = 0.94, P < 2.2 × 1016) and also have a significant positive correlation withsomeremote functional DNA elements like enhancers and promoters (Enhancer: hESC: r=0.997, P=2.3×10−4; IMR90: r=0.934, P=2×10−2; Promoter: hESC: r = 0.995, P = 3.8 × 10−4; IMR90: r = 0.996, P = 3.2 × 10−4). Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes

The fading of reported effectiveness. A meta-analysis of randomised controlled trials

BACKGROUND: The "real" effect size of a medical therapy is constant over time. In contrast, the effect size reported in randomised controlled trials (RCTs) may change over time because the sum of all kinds of bias influencing the reported effectiveness is not necessarily constant. As this would affect the validity of meta-analyses, we tested the hypothesis that the reported effect size decreases over time. Furthermore, we tested three hypotheses that would explain a possible change. METHODS: Because of well established outcome measures, the lipid-lowering drugs Pravastatin and Atorvastatin (serum low-density lipoprotein cholesterol, LDL-C) and the anti-glaucoma drugs Timolol and Latanoprost (intraocular pressure, IOP) were chosen for this investigation. Studies were identified by a standardized MEDLINE search. RCTs investigating the above identified medications administered as monotherapy, and in defined dosages, were included. Publication year, baseline (= pre-treatment value in the treatment group of interest) and post intervention means, number of patients and the assignment to experimental or control group were extracted for each study. RESULTS: A total of 625 citations were screened; 206 met the inclusion criteria. The reported effect size of Pravastatin (change of reported effect size in five years: -3.22% LDL-C, P < .0001), Timolol (-0.56 mmHg, P < .0001) and Latanoprost (-1.78 mmHg, P = .0074) decreased over time, while there was no significant change for Atorvastatin (+0.31% LDL-C, P = .8618). Multiple regression analysis showed that baseline values were the most important influencing factor; study size or treatment group did not play a significant role. CONCLUSION: The effectiveness of medical therapies reported in RCTs decreases over time in three of the four investigated pharmaceuticals, caused mainly by baseline differences. We call this phenomenon "fading of reported effectiveness". Under this condition the validity of a meta-analysis may be impaired. Therefore we propose to observe this phenomenon in future meta-analyses in order to guarantee a maximum of transparency

Sexual conflict maintains variation at an insecticide resistance locus

Background: The maintenance of genetic variation through sexually antagonistic selection is controversial, partly because specific sexually-antagonistic alleles have not been identified. The Drosophila DDT resistance allele (DDT-R) is an exception. This allele increases female fitness, but simultaneously decreases male fitness, and it has been suggested that this sexual antagonism could explain why polymorphism was maintained at the locus prior to DDT use. We tested this possibility using a genetic model and then used evolving fly populations to test model predictions. Results: Theory predicted that sexual antagonism is able to maintain genetic variation at this locus, hence explaining why DDT-R did not fix prior to DDT use despite increasing female fitness, and experimentally evolving fly populations verified theoretical predictions. Conclusions: This demonstrates that sexually antagonistic selection can maintain genetic variation and explains the DDT-R frequencies observed in nature

Evolutionary Dynamics of the Ty3/Gypsy LTR Retrotransposons in the Genome of Anopheles gambiae

Ty3/gypsy elements represent one of the most abundant and diverse LTR-retrotransposon (LTRr) groups in the Anopheles gambiae genome, but their evolutionary dynamics have not been explored in detail. Here, we conduct an in silico analysis of the distribution and abundance of the full complement of 1045 copies in the updated AgamP3 assembly. Chromosomal distribution of Ty3/gypsy elements is inversely related to arm length, with densities being greatest on the X, and greater on the short versus long arms of both autosomes. Taking into account the different heterochromatic and euchromatic compartments of the genome, our data suggest that the relative abundance of Ty3/gypsy LTRrs along each chromosome arm is determined mainly by the different proportions of heterochromatin, particularly pericentric heterochromatin, relative to total arm length. Additionally, the breakpoint regions of chromosomal inversion 2La appears to be a haven for LTRrs. These elements are underrepresented more than 7-fold in euchromatin, where 33% of the Ty3/gypsy copies are associated with genes. The euchromatin on chromosome 3R shows a faster turnover rate of Ty3/gypsy elements, characterized by a deficit of proviral sequences and the lowest average sequence divergence of any autosomal region analyzed in this study. This probably reflects a principal role of purifying selection against insertion for the preservation of longer conserved syntenyc blocks with adaptive importance located in 3R. Although some Ty3/gypsy LTRrs show evidence of recent activity, an important fraction are inactive remnants of relatively ancient insertions apparently subject to genetic drift. Consistent with these computational predictions, an analysis of the occupancy rate of putatively older insertions in natural populations suggested that the degenerate copies have been fixed across the species range in this mosquito, and also are shared with the sibling species Anopheles arabiensis

Coexistence of Trichome Variation in a Natural Plant Population: A Combined Study Using Ecological and Candidate Gene Approaches

The coexistence of distinct phenotypes within populations has long been investigated in evolutionary ecology. Recent studies have identified the genetic basis of distinct phenotypes, but it is poorly understood how the variation in candidate loci is maintained in natural environments. In this study, we examined fitness consequences and genetic basis of variation in trichome production in a natural population of Arabidopsis halleri subsp. gemmifera. Half of the individuals in the study population produced trichomes while the other half were glabrous, and the leaf beetle Phaedon brassicae imposed intensive damage to both phenotypes. The fitness of hairy and glabrous plants showed no significant differences in the field during two years. A similar result was obtained when sibling hairy and glabrous plants were transplanted at the same field site, whereas a fitness cost of trichome production was detected under a weak herbivory condition. Thus, equivalent fitness of hairy and glabrous plants under natural herbivory allows their coexistence in the contemporary population. The pattern of polymorphism of the candidate trichome gene GLABROUS1 (GL1) showed no evidence of long-term maintenance of trichome variation within the population. Although balancing selection under fluctuating biotic environments is often proposed to explain the maintenance of defense variation, the lack of clear evidence of balancing selection in the study population suggests that other factors such as gene flow and neutral process may have played relatively large roles in shaping trichome variation at least for the single population level

Mosquitoes LTR Retrotransposons: A Deeper View into the Genomic Sequence of Culex quinquefasciatus

A set of 67 novel LTR-retrotransposon has been identified by in silico analyses of the Culex quinquefasciatus genome using the LTR_STRUC program. The phylogenetic analysis shows that 29 novel and putatively functional LTR-retrotransposons detected belong to the Ty3/gypsy group. Our results demonstrate that, by considering only families containing potentially autonomous LTR-retrotransposons, they account for about 1% of the genome of C. quinquefasciatus. In previous studies it has been estimated that 29% of the genome of C. quinquefasciatus is occupied by mobile genetic elements