Highly accurate calculations of the rotationally excited bound states in three-body systems

An effective optimization strategy has been developed to construct highly accurate bound state wave functions in various three-body systems. Our procedure appears to be very effective for computations of weakly bound states and various excited states, including rotationally excited states, i.e. states with $L \ge 1$. The efficiency of our procedure is illustrated by computations of the excited $P^{*}(L = 1)-$states in the $dd\mu, dt\mu$ and $tt\mu$ muonic molecular ions, $P(L = 1)-$states in the non-symmetric $pd\mu, pt\mu$ and $dt\mu$ ions and $2^{1}P(L = 1)-$ and $2^{3}P(L = 1)-$states in He atom(s)

Proton spectroscopic imaging of brain metabolites in basal ganglia of healthy older adults

Object: We sought to measure brain metabolite levels in healthy older people. Materials and methods: Spectroscopic imaging at the level of the basal ganglia was applied in 40 participants aged 73–74 years. Levels of the metabolites N-acetyl aspartate (NAA), choline, and creatine were determined in "institutional units" (IU) corrected for T1 and T2 relaxation effects. Structural imaging enabled determination of grey matter (GM), white matter (WM), and cerebrospinal fluid content. ANOVA analysis was carried out for voxels satisfying quality criteria. Results: Creatine levels were greater in GM than WM (57 vs. 44 IU, p < 0.001), whereas choline and NAA levels were greater in WM than GM [13 vs. 10 IU (p < 0.001) and 76 versus 70 IU (p = 0.03), respectively]. The ratio of NAA/cre was greater in WM than GM (2.1 vs. 1.4, p = 0.001) as was that of cho/cre (0.32 vs. 0.16, p < 0.001). A low voxel yield was due to brain atrophy and the difficulties of shimming over an extended region of brain. Conclusion: This study addresses the current lack of information on brain metabolite levels in older adults. The normal features of ageing result in a substantial loss of reliable voxels and should be taken into account when planning studies. Improvements in shimming are also required before the methods can be applied more widely

The Brain Health Index: Towards a combined measure of neurovascular and neurodegenerative structural brain injury

Background: A structural magnetic resonance imaging measure of combined neurovascular and neurodegenerative burden may be useful as these features often coexist in older people, stroke and dementia. Aim: We aimed to develop a new automated approach for quantifying visible brain injury from small vessel disease and brain atrophy in a single measure, the brain health index. Materials and methods: We computed brain health index in N = 288 participants using voxel-based Gaussian mixture model cluster analysis of T1, T2, T2*, and FLAIR magnetic resonance imaging. We tested brain health index against a validated total small vessel disease visual score and white matter hyperintensity volumes in two patient groups (minor stroke, N = 157; lupus, N = 51) and against measures of brain atrophy in healthy participants (N = 80) using multiple regression. We evaluated associations with Addenbrooke’s Cognitive Exam Revised in patients and with reaction time in healthy participants. Results: The brain health index (standard beta = 0.20–0.59, P &#60; 0.05) was significantly and more strongly associated with Addenbrooke’s Cognitive Exam Revised, including at one year follow-up, than white matter hyperintensity volume (standard beta = 0.04–0.08, P &#62; 0.05) and small vessel disease score (standard beta = 0.02–0.27, P &#62; 0.05) alone in both patient groups. Further, the brain health index (standard beta = 0.57–0.59, P &#60; 0.05) was more strongly associated with reaction time than measures of brain atrophy alone (standard beta = 0.04–0.13, P &#62; 0.05) in healthy participants. Conclusions: The brain health index is a new image analysis approach that may usefully capture combined visible brain damage in large-scale studies of ageing, neurovascular and neurodegenerative disease

Impact of small vessel disease in the brain on gait and balance

Gait and balance impairment is highly prevalent in older people. We aimed to assess whether and how single markers of small vessel disease (SVD) or a combination thereof explain gait and balance function in the elderly. We analysed 678 community-dwelling healthy subjects from the Lothian Birth Cohort 1936 at the age of 71–74 years who had undergone comprehensive risk factor assessment, gait and balance assessment as well as brain MRI. We investigated the impact of individual SVD markers (white matter hyperintensity – WMH, microbleeds, lacunes, enlarged perivascular spaces, brain atrophy) as seen on structural brain MRI and of a global SVD score on the patients’ performance. A regression model revealed that age, sex, and hypertension significantly explained gait speed. Among SVD markers white matter hyperintensity (WMH) score or volume were additional significant and independent predictors of gait speed in the regression model. A similar association was seen with the global SVD score. Our study confirms a negative impact of SVD-related morphologic brain changes on gait speed in addition to age, sex and hypertension independent from brain atrophy. The presence of WMH seems to be the major driving force for SVD on gait impairment in healthy elderly subjects

Genetic determinants of cortical structure (thickness, surface area and volumes) among disease free adults in the CHARGE Consortium

Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

Protocol for the perfusion and angiography imaging sub-study of the Third International Stroke Trial (IST-3) of alteplase treatment within six-hours of acute ischemic stroke

RATIONALE: Intravenous thrombolysis with recombinant tissue Plasminogen Activator improves outcomes in patients treated early after stroke but at the risk of causing intracranial hemorrhage. Restricting recombinant tissue Plasminogen Activator use to patients with evidence of still salvageable tissue, or with definite arterial occlusion, might help reduce risk, increase benefit and identify patients for treatment at late time windows. AIMS: To determine if perfusion or angiographic imaging with computed tomography or magnetic resonance help identify patients who are more likely to benefit from recombinant tissue Plasminogen Activator in the context of a large multicenter randomized trial of recombinant tissue Plasminogen Activator given within six-hours of onset of acute ischemic stroke, the Third International Stroke Trial. DESIGN: Third International Stroke Trial is a prospective multicenter randomized controlled trial testing recombinant tissue Plasminogen Activator (0·9 mg/kg, maximum dose 90 mg) started up to six-hours after onset of acute ischemic stroke, in patients with no clear indication for or contraindication to recombinant tissue Plasminogen Activator. Brain imaging (computed tomography or magnetic resonance) was mandatory pre-randomization to exclude hemorrhage. Scans were read centrally, blinded to treatment and clinical information. In centers where perfusion and/or angiography imaging were used routinely in stroke, these images were also collected centrally, processed and assessed using validated visual scores and computational measures. STUDY OUTCOMES: The primary outcome in Third International Stroke Trial is alive and independent (Oxford Handicap Score 0-2) at 6 months; secondary outcomes are symptomatic and fatal intracranial hemorrhage, early and late death. The perfusion and angiography study additionally will examine interactions between recombinant tissue Plasminogen Activator and clinical outcomes, infarct growth and recanalization in the presence or absence of perfusion lesions and/or arterial occlusion at presentation. The study is registered ISRCTN25765518

The role of ALOX5AP, LTA4H and LTB4R polymorphisms in determining baseline lung function and COPD susceptibility in UK smokers

<p>Abstract</p> <p>Background</p> <p>We have previously shown evidence that polymorphisms within genes controlling leukotriene B₄(LTB₄) production (<it>ALOX5AP </it>and <it>LTA4H</it>) are associated with asthma susceptibility in children. Evidence also suggests a potential role of LTB₄in COPD disease mechanisms including recruitment of neutrophils to the lung. The aim of the current study was to see if these SNPs and those spanning the receptor genes for LTB₄(<it>LTB4R1 </it>and <it>LTB4R2</it>) influence baseline lung function and COPD susceptibility/severity in smokers.</p> <p>Methods</p> <p>Eight <it>ALOX5AP</it>, six <it>LTA4H </it>and six <it>LTB4R </it>single nucleotide polymorphisms (SNPs) were genotyped in a UK Smoking Cohort (n = 992). Association with baseline lung function (FEV₁and FEV₁/FVC ratio) was determined by linear regression. Logistic regression was used to compare smoking controls (n = 176) with spirometry-defined COPD cases (n = 599) and to more severe COPD cases (GOLD stage 3 and 4, n = 389).</p> <p>Results</p> <p>No association with <it>ALOX5AP</it>, <it>LTA4H </it>or <it>LTB4R </it>survived correction for multiple testing. However, we showed modest association with <it>LTA4H </it>rs1978331C (intron 11) with increased FEV₁(p = 0.029) and with increased FEV₁/FVC ratio (p = 0.020).</p> <p>Conclusions</p> <p>These data suggest that polymorphisms spanning <it>ALOX5AP</it>, <it>LTA4H </it>and the <it>LTB4R </it>locus are not major determinants of baseline lung function in smokers, but provide tentative evidence for <it>LTA4H </it>rs1978331C (intron 11) in determining baseline FEV₁and FEV₁/FVC ratio in Caucasian Smokers in addition to our previously identified role in asthma susceptibility.</p