The Population Genetics of Pseudomonas aeruginosa Isolates from Different Patient Populations Exhibits High-Level Host Specificity

Objective To determine whether highly prevalent P. aeruginosa sequence types (ST) in Dutch cystic fibrosis (CF) patients are specifically linked to CF patients we investigated the population structure of P. aeruginosa from different clinical backgrounds. We first selected the optimal genotyping method by comparing pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and multilocus variable number tandem-repeat analysis (MLVA). Methods Selected P. aeruginosa isolates (n = 60) were genotyped with PFGE, MLST and MLVA to determine the diversity index (DI) and congruence (adjusted Rand and Wallace coefficients). Subsequently, isolates from patients admitted to two different ICUs (n = 205), from CF patients (n = 100) and from non-ICU, non-CF patients (n = 58, of which 19 were community acquired) were genotyped with MLVA to determine distribution of genotypes and genetic diversity. Results Congruence between the typing methods was >79% and DIs were similar and all >0.963. Based on costs, ease, speed and possibilities to compare results between labs an adapted MLVA scheme called MLVA9-Utrecht was selected as the preferred typing method. In 363 clinical isolates 252 different MLVA types (MTs) were identified, indicating a highly diverse population (DI = 0.995; CI = 0.993–0.997). DI levels were similarly high in the diverse clinical sources (all >0.981) and only eight genotypes were shared. MTs were highly specific (>80%) for the different patient populations, even for similar patient groups (ICU patients) in two distinct geographic regions, with only three of 142 ICU genotypes detected in both ICUs. The two major CF clones were unique to CF patients. Conclusion The population structure of P. aeruginosa isolates is highly diverse and population specific without evidence for a core lineage in which major CF, hospital or community clones co-cluster. The two genotypes highly prevalent among Dutch CF patients appeared unique to CF patients, suggesting specific adaptation of these clones to the CF lung

Synthesis of Tapered CdS Nanobelts and CdSe Nanowires with Good Optical Property by Hydrogen-Assisted Thermal Evaporation

The tapered CdS nanobelts and CdSe nanowires were prepared by hydrogen-assisted thermal evaporation method. Different supersaturation leads to two different kinds of 1D nanostructures. The PL measurements recorded from the as-prepared tapered CdS nanobelts and CdSe nanowires show only a bandgap emission with relatively narrow full-width half maximum, which means that they possess good optical property. The as-synthesized high-quality tapered CdS nanobelts and CdSe nanowires may be excellent building blocks for photonic devices

Diagnostic accuracy of plasma NT-proBNP levels for excluding cardiac abnormalities in the very elderly

<p>Abstract</p> <p>Background</p> <p>In the elderly the diagnosis of chronic heart failure is often challenging and the availability of echocardiography can be limited. Plasma levels of NT-proBNP are valuable tools to diagnose patients with heart failure. However, the performance of this biomarker to detect cardiac abnormalities in the very elderly remains unclear. The aims of this study were to investigate the relation between NT-proBNP and cardiac abnormalities and to evaluate the use of NT-proBNP to exclude structural and functional cardiac abnormalities in a community-based sample of "well-functioning" nonagenarians.</p> <p>Methods</p> <p>A diagnostic cross-sectional study embedded within the Leiden 85-plus Study in the municipality of Leiden, the Netherlands. Plasma NT-proBNP levels were measured and 2-dimensional echocardiography was performed in a subgroup of 80 well-functioning nonagenarians. Linear regression analysis was used to explore the relation between NT-proBNP and cardiac abnormalities and ROC curve analysis was used to assess the performance of NT-proBNP to exclude cardiac abnormalities. The upper limit of the lowest tertile of NT-proBNP was used as a cut-off value.</p> <p>Results</p> <p>NT-proBNP levels were associated with abnormal left ventricular (LV) dimensions, LV systolic and diastolic function, left atrial enlargement and valvular heart disease. LV mass, E/A ratio and degree of aortic regurgitation were identified as independent predictors of NT-proBNP. NT-proBNP levels were higher with greater number of echocardiographic abnormalities (P < 0.001). A cut-off level of 269.5 pg/mL identified patients with abnormal LV dimensions or depressed LV systolic function (sensitivity 85%, negative predictive value (NPV) 77%, area under the curve 0.75 (95% CI 0.64-0.85)). In addition, high NPV were found for LV systolic dysfunction, left atrial enlargement, severe valvular heart disease and pulmonary hypertension. The test performance of NT-proBNP to exclude any echocardiographic abnormality showed a sensitivity of 82% and a NPV of 65%.</p> <p>Conclusions</p> <p>In this convenience sample of well-functioning nonagenarians NT-proBNP was related to a wide variety of functional and structural echocardiographic abnormalities. Moreover, NT-proBNP could be used to exclude echocardiographic abnormalities in well-functioning nonagenarians and might be used to indicate who needs to be referred for further cardiovascular examination.</p

The effect of social context on the use of visual information

Social context modulates action kinematics. Less is known about whether social context also affects the use of task relevant visual information. We tested this hypothesis by examining whether the instruction to play table tennis competitively or cooperatively affected the kind of visual cues necessary for successful table tennis performance. In two experiments, participants played table tennis in a dark room with only the ball, net, and table visible. Visual information about both players’ actions was manipulated by means of self-glowing markers. We recorded the number of successful passes for each player individually. The results showed that participants’ performance increased when their own body was rendered visible in both the cooperative and the competitive condition. However, social context modulated the importance of different sources of visual information about the other player. In the cooperative condition, seeing the other player’s racket had the largest effects on performance increase, whereas in the competitive condition, seeing the other player’s body resulted in the largest performance increase. These results suggest that social context selectively modulates the use of visual information about others’ actions in social interactions

Non-monotonicity on a spatio-temporally defined cyclic task: evidence of two movement types?

We tested 23 healthy participants who performed rhythmic horizontal movements of the elbow. The required amplitude and frequency ranges of the movements were specified to the participants using a closed shape on a phase-plane display, showing angular velocity versus angular position, such that participants had to continuously control both the speed and the displacement of their forearm. We found that the combined accuracy in velocity and position throughout the movement was not a monotonic function of movement speed. Our findings suggest that specific combinations of required movement frequency and amplitude give rise to two distinct types of movements: one of a more rhythmic nature, and the other of a more discrete nature

Determinants of the Spatiotemporal Dynamics of the 2009 H1N1 Pandemic in Europe: Implications for Real-Time Modelling

Influenza pandemics in the last century were characterized by successive waves and differences in impact and timing between different regions, for reasons not clearly understood. The 2009 H1N1 pandemic showed rapid global spread, but with substantial heterogeneity in timing within each hemisphere. Even within Europe substantial variation was observed, with the UK being unique in experiencing a major first wave of transmission in early summer and all other countries having a single major epidemic in the autumn/winter, with a West to East pattern of spread. Here we show that a microsimulation model, parameterised using data about H1N1pdm collected by the beginning of June 2009, explains the occurrence of two waves in UK and a single wave in the rest of Europe as a consequence of timing of H1N1pdm spread, fluxes of travels from US and Mexico, and timing of school vacations. The model provides a description of pandemic spread through Europe, depending on intra-European mobility patterns and socio-demographic structure of the European populations, which is in broad agreement with observed timing of the pandemic in different countries. Attack rates are predicted to depend on the socio-demographic structure, with age dependent attack rates broadly agreeing with available serological data. Results suggest that the observed heterogeneity can be partly explained by the between country differences in Europe: marked differences in school calendars, mobility patterns and sociodemographic structures. Moreover, higher susceptibility of children to infection played a key role in determining the epidemiology of the 2009 pandemic. Our work shows that it would have been possible to obtain a broad-brush prediction of timing of the European pandemic well before the autumn of 2009, much more difficult to achieve with simpler models or pre-pandemic parameterisation. This supports the use of models accounting for the structure of complex modern societies for giving insight to policy makers

Variant location is a novel risk factor for individuals with arrhythmogenic cardiomyopathy due to a desmoplakin (DSP) truncating variant.

BACKGROUND: Truncating variants in desmoplakin (DSPtv) are an important cause of arrhythmogenic cardiomyopathy; however the genetic architecture and genotype-specific risk factors are incompletely understood. We evaluated phenotype, risk factors for ventricular arrhythmias, and underlying genetics of DSPtv cardiomyopathy. METHODS: Individuals with DSPtv and any cardiac phenotype, and their gene-positive family members were included from multiple international centers. Clinical data and family history information were collected. Event-free survival from ventricular arrhythmia was assessed. Variant location was compared between cases and controls, and literature review of reported DSPtv performed. RESULTS: There were 98 probands and 72 family members (mean age at diagnosis 43±8 years, 59% women) with a DSPtv, of which 146 were considered clinically affected. Ventricular arrhythmia (sudden cardiac arrest, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy) occurred in 56 (33%) individuals. DSPtv location and proband status were independent risk factors for ventricular arrhythmia. Further, gene region was important with variants in cases (cohort n=98; Clinvar n=167) more likely to occur in the regions resulting in nonsense mediated decay of both major DSP isoforms, compared with n=124 genome aggregation database control variants (148 [83.6%] versus 29 [16.4%]; P<0.0001). CONCLUSIONS: In the largest series of individuals with DSPtv, we demonstrate that variant location is a novel risk factor for ventricular arrhythmia, can inform variant interpretation, and provide critical insights to allow for precision-based clinical management

Grasping Kinematics from the Perspective of the Individual Digits: A Modelling Study

Grasping is a prototype of human motor coordination. Nevertheless, it is not known what determines the typical movement patterns of grasping. One way to approach this issue is by building models. We developed a model based on the movements of the individual digits. In our model the following objectives were taken into account for each digit: move smoothly to the preselected goal position on the object without hitting other surfaces, arrive at about the same time as the other digit and never move too far from the other digit. These objectives were implemented by regarding the tips of the digits as point masses with a spring between them, each attracted to its goal position and repelled from objects' surfaces. Their movements were damped. Using a single set of parameters, our model can reproduce a wider variety of experimental findings than any previous model of grasping. Apart from reproducing known effects (even the angles under which digits approach trapezoidal objects' surfaces, which no other model can explain), our model predicted that the increase in maximum grip aperture with object size should be greater for blocks than for cylinders. A survey of the literature shows that this is indeed how humans behave. The model can also adequately predict how single digit pointing movements are made. This supports the idea that grasping kinematics follow from the movements of the individual digits

Can cognitive enhancers reduce the risk of falls in older people with Mild Cognitive Impairment? A protocol for a randomised controlled double blind trial

<p>Abstract</p> <p>Background</p> <p>Older adults with cognitive problems have a higher risk of falls, at least twice that of cognitively normal older adults. The consequences of falls in this population are very serious: fallers with cognitive problems suffer more injuries due to falls and are approximately five times more likely to be admitted to institutional care. Although the mechanisms of increased fall risk in cognitively impaired people are not completely understood, it is known that impaired cognitive abilities can reduce attentional resource allocation while walking. Since cognitive enhancers, such as cholinesterase inhibitors, improve attention and executive function, we hypothesise that cognitive enhancers may reduce fall risk in elderly people in the early stages of cognitive decline by improving their gait and balance performance due to an enhancement in attention and executive function.</p> <p>Method/Design</p> <p>Double blinded randomized controlled trial with 6 months follow-up in 140 older individuals with Mild Cognitive Impairment (MCI). Participants will be randomized to the intervention group, receiving donepezil, and to the control group, receiving placebo. A block randomization by four and stratification based on fall history will be performed. Primary outcomes are improvements in gait velocity and reduction in gait variability. Secondary outcomes are changes in the balance confidence, balance sway, attention, executive function, and number of falls.</p> <p>Discussion</p> <p>By characterizing and understanding the effects of cognitive enhancers on fall risk in older adults with cognitive impairments, we will be able to pave the way for a new approach to fall prevention in this population. This RCT study will provide, for the first time, information regarding the effect of a medication designed to augment cognitive functioning have on the risk of falls in older adults with Mild Cognitive Impairment. We expect a significant reduction in the risk of falls in this vulnerable population as a function of the reduced gait variability achieved by treatment with cognitive enhancers. This study may contribute to a new approach to prevent and treat fall risk in seniors in early stages of dementia.</p> <p>Trial Registration</p> <p>The protocol for this study is registered with the Clinical Trials Registry, identifier number: NCT00934531 <url>http://www.clinicaltrials.gov</url></p

Characterizing the Epidemiology of the 2009 Influenza A/H1N1 Pandemic in Mexico

Gerardo Chowell and colleagues address whether school closures and other social distancing strategies were successful in reducing pandemic flu transmission in Mexico by analyzing the age- and state-specific incidence of influenza morbidity and mortality in 32 Mexican states