Senescence rates are determined by ranking on the fast-slow life-history continuum.

Comparative analyses of survival senescence by using life tables have identified generalizations including the observation that mammals senesce faster than similar-sized birds. These generalizations have been challenged because of limitations of life-table approaches and the growing appreciation that senescence is more than an increasing probability of death. Without using life tables, we examine senescence rates in annual individual fitness using 20 individual-based data sets of terrestrial vertebrates with contrasting life histories and body size. We find that senescence is widespread in the wild and equally likely to occur in survival and reproduction. Additionally, mammals senesce faster than birds because they have a faster life history for a given body size. By allowing us to disentangle the effects of two major fitness components our methods allow an assessment of the robustness of the prevalent life-table approach. Focusing on one aspect of life history - survival or recruitment - can provide reliable information on overall senescence.

Benchmarking therapeutic drug monitoring software: A review of available computer tools

Therapeutic drug monitoring (TDM) aims to optimize treatments by individualizing dosage regimens based on the measurement of blood concentrations. Dosage individualization to maintain concentrations within a target range requires pharmacokinetic and clinical capabilities. Bayesian calculations currently represent the gold standard TDM approach but require computation assistance. In recent decades computer programs have been developed to assist clinicians in this assignment. The aim of this survey was to assess and compare computer tools designed to support TDM clinical activities. The literature and the Internet were searched to identify software. All programs were tested on personal computers. Each program was scored against a standardized grid covering pharmacokinetic relevance, user friendliness, computing aspects, interfacing and storage. A weighting factor was applied to each criterion of the grid to account for its relative importance. To assess the robustness of the software, six representative clinical vignettes were processed through each of them. Altogether, 12 software tools were identified, tested and ranked, representing a comprehensive review of the available software. Numbers of drugs handled by the software vary widely (from two to 180), and eight programs offer users the possibility of adding new drug models based on population pharmacokinetic analyses. Bayesian computation to predict dosage adaptation from blood concentration (a posteriori adjustment) is performed by ten tools, while nine are also able to propose a priori dosage regimens, based only on individual patient covariates such as age, sex and bodyweight. Among those applying Bayesian calculation, MM-USC*PACK© uses the non-parametric approach. The top two programs emerging from this benchmark were MwPharm© and TCIWorks. Most other programs evaluated had good potential while being less sophisticated or less user friendly. Programs vary in complexity and might not fit all healthcare settings. Each software tool must therefore be regarded with respect to the individual needs of hospitals or clinicians. Programs should be easy and fast for routine activities, including for non-experienced users. Computer-assisted TDM is gaining growing interest and should further improve, especially in terms of information system interfacing, user friendliness, data storage capability and report generation.

Chirurgie

2007 was marked by a growing trend towards minimal invasive surgery and enhanced recovery, especially in visceral surgery. In comparison to the laparoscopic revolution in the eighties, Natural orifice transluminal endoscopic surgery (NOTES) must be watched on closely, and will probably have to be taken into account in a near future. Minimal invasive procedures in oesophageal cancer surgery have proved both efficient and oncologically safe. Implementation of Fast track protocols now permits a much faster patient's return to normal daily activity. In hepatobiliary and pancreatic surgery, multidisciplinary efforts have been done to better select patients, widen the indications and increase efficiency.

Cardiopathies congénitales de l'âge adulte: nouvelle population de patients, prise en charge multidisciplinaire [Adults with congenital heart diseases: a growing population, a multidisciplinary approach].

Untill recently, congenital heart disease was considered as a childhood's disease. With improvement in pediatric survival, adults with a congenital heart disease (ACHD) represent an emerging group of patients who need specialized medical care. In 2010, the ESC published newguidelines on global and specific management of adults with congenital heart disease. ACHD centers organize appropriate medical care for these patients, promote specialist training and national scientific research in collaboration with other national ACHD centers.

Fast screening and confirmation of doping agents by UHPLC-QTOF-MS/MS

Introduction: The general strategy to perform anti-doping analysis starts with a screening followed by a confirmatory step when a sample is suspected to be positive. The screening step should be fast, generic and able to highlight any sample that may contain a prohibited substance by avoiding false negative and reducing false positive results. The confirmatory step is a dedicated procedure comprising a selective sample preparation and detection mode. Aim: The purpose of the study is to develop rapid screening and selective confirmatory strategies to detect and identify 103 doping agents in urine. Methods: For the screening, urine samples were simply diluted by a factor 2 with ultra-pure water and directly injected ("dilute and shoot") in the ultrahigh- pressure liquid chromatography (UHPLC). The UHPLC separation was performed in two gradients (ESI positive and negative) from 5/95 to 95/5% of MeCN/Water containing 0.1% formic acid. The gradient analysis time is 9 min including 3 min reequilibration. Analytes detection was performed in full scan mode on a quadrupole time-of-flight (QTOF) mass spectrometer by acquiring the exact mass of the protonated (ESI positive) or deprotonated (ESI negative) molecular ion. For the confirmatory analysis, urine samples were extracted on SPE 96-well plate with mixed-mode cation (MCX) for basic and neutral compounds or anion exchange (MAX) sorbents for acidic molecules. The analytes were eluted in 3 min (including 1.5 min reequilibration) with a S1-25 Ann Toxicol Anal. 2009; 21(S1) Abstracts gradient from 5/95 to 95/5% of MeCN/Water containing 0.1% formic acid. Analytes confirmation was performed in MS and MS/MS mode on a QTOF mass spectrometer. Results: In the screening and confirmatory analysis, basic and neutral analytes were analysed in the positive ESI mode, whereas acidic compounds were analysed in the negative mode. The analyte identification was based on retention time (tR) and exact mass measurement. "Dilute and shoot" was used as a generic sample treatment in the screening procedure, but matrix effect (e.g., ion suppression) cannot be avoided. However, the sensitivity was sufficient for all analytes to reach the minimal required performance limit (MRPL) required by the World Anti Doping Agency (WADA). To avoid time-consuming confirmatory analysis of false positive samples, a pre-confirmatory step was added. It consists of the sample re-injection, the acquisition of MS/MS spectra and the comparison to reference material. For the confirmatory analysis, urine samples were extracted by SPE allowing a pre-concentration of the analyte. A fast chromatographic separation was developed as a single analyte has to be confirmed. A dedicated QTOF-MS and MS/MS acquisition was performed to acquire within the same run a parallel scanning of two functions. Low collision energy was applied in the first channel to obtain the protonated molecular ion (QTOF-MS), while dedicated collision energy was set in the second channel to obtain fragmented ions (QTOF-MS/MS). Enough identification points were obtained to compare the spectra with reference material and negative urine sample. Finally, the entire process was validated and matrix effects quantified. Conclusion: Thanks to the coupling of UHPLC with the QTOF mass spectrometer, high tR repeatability, sensitivity, mass accuracy and mass resolution over a broad mass range were obtained. The method was sensitive, robust and reliable enough to detect and identify doping agents in urine. Keywords: screening, confirmatory analysis, UHPLC, QTOF, doping agents

Cost evaluation of cardiovascular magnetic resonance versus coronary angiography for the diagnostic work-up of coronary artery disease: Application of the European Cardiovascular Magnetic Resonance registry data to the German, United Kingdom, Swiss, and United States health care systems.

ABSTRACT: BACKGROUND: Cardiovascular magnetic resonance (CMR) has favorable characteristics for diagnostic evaluation and risk stratification of patients with known or suspected CAD. CMR utilization in CAD detection is growing fast. However, data on its cost-effectiveness are scarce. The goal of this study is to compare the costs of two strategies for detection of significant coronary artery stenoses in patients with suspected coronary artery disease (CAD): 1) Performing CMR first to assess myocardial ischemia and/or infarct scar before referring positive patients (defined as presence of ischemia and/or infarct scar to coronary angiography (CXA) versus 2) a hypothetical CXA performed in all patients as a single test to detect CAD. METHODS: A subgroup of the European CMR pilot registry was used including 2,717 consecutive patients who underwent stress-CMR. From these patients, 21% were positive for CAD (ischemia and/or infarct scar), 73% negative, and 6% uncertain and underwent additional testing. The diagnostic costs were evaluated using invoicing costs of each test performed. Costs analysis was performed from a health care payer perspective in German, United Kingdom, Swiss, and United States health care settings. RESULTS: In the public sectors of the German, United Kingdom, and Swiss health care systems, cost savings from the CMR-driven strategy were 50%, 25% and 23%, respectively, versus outpatient CXA. If CXA was carried out as an inpatient procedure, cost savings were 46%, 50% and 48%, respectively. In the United States context, cost savings were 51% when compared with inpatient CXA, but higher for CMR by 8% versus outpatient CXA. CONCLUSION: This analysis suggests that from an economic perspective, the use of CMR should be encouraged as a management option for patients with suspected CAD.

A one-year monitoring of nicotine use in sport: frontier between potential performance enhancement and addiction issues.

Tobacco consumption is a global epidemic responsible for a vast burden of disease. With pharmacological properties sought-after by consumers and responsible for addiction issues, nicotine is the main reason of this phenomenon. Accordingly, smokeless tobacco products are of growing popularity in sport owing to potential performance enhancing properties and absence of adverse effects on the respiratory system. Nevertheless, nicotine does not appear on the 2011 World Anti-Doping Agency (WADA) Prohibited List or Monitoring Program by lack of a comprehensive large-scale prevalence survey. Thus, this work describes a one-year monitoring study on urine specimens from professional athletes of different disciplines covering 2010 and 2011. A method for the detection and quantification of nicotine, its major metabolites (cotinine, trans-3-hydroxycotinine, nicotine-N'-oxide and cotinine-N-oxide) and minor tobacco alkaloids (anabasine, anatabine and nornicotine) was developed, relying on ultra-high pressure liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-TQ-MS/MS). A simple and fast dilute-and-shoot sample treatment was performed, followed by hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS) operated in positive electrospray ionization (ESI) mode with multiple reaction monitoring (MRM) data acquisition. After method validation, assessing the prevalence of nicotine consumption in sport involved analysis of 2185 urine samples, accounting for 43 different sports. Concentrations distribution of major nicotine metabolites, minor nicotine metabolites and tobacco alkaloids ranged from 10 (LLOQ) to 32,223, 6670 and 538 ng/mL, respectively. Compounds of interest were detected in trace levels in 23.0% of urine specimens, with concentration levels corresponding to an exposure within the last three days for 18.3% of samples. Likewise, hypothesizing conservative concentration limits for active nicotine consumption prior and/or during sport practice (50 ng/mL for nicotine, cotinine and trans-3-hydroxycotinine and 25 ng/mL for nicotine-N'-oxide, cotinine-N-oxide, anabasine, anatabine and nornicotine) revealed a prevalence of 15.3% amongst athletes. While this number may appear lower than the worldwide smoking prevalence of around 25%, focusing the study on selected sports highlighted more alarming findings. Indeed, active nicotine consumption in ice hockey, skiing, biathlon, bobsleigh, skating, football, basketball, volleyball, rugby, American football, wrestling and gymnastics was found to range between 19.0 and 55.6%. Therefore, considering the adverse effects of smoking on the respiratory tract and numerous health threats detrimental to sport practice at top level, likelihood of smokeless tobacco consumption for performance enhancement is greatly supported.

Growing up with bilateral hippocampal atrophy: from childhood to teenage.

The respective roles of the medial temporal lobe (MTL) structures in memory are controversial. Some authors put forward a modular account according to which episodic memory and recollection-based processes are crucially dependent on the hippocampal formation whereas semantic acquisition and familiarity-based processes rely on the adjacent parahippocampal gyri. Others defend a unitary view. We report the case of VJ, a boy with developmental amnesia of most likely perinatal onset diagnosed at the age of 8. Magnetic resonance imaging (MRI), including quantitative volumetric measurements of the hippocampal formation and of the entorhinal, perirhinal, and temporopolar cortices, showed severe, bilateral atrophy of the hippocampal formation, fornix and mammillary bodies; by contrast, the perirhinal cortex was within normal range and the entorhinal and temporopolar cortex remained within two standard deviations (SDs) from controls' mean. We examined the development of his semantic knowledge from childhood to teenage as well as his recognition and cued recall memory abilities. On tasks tapping semantic memory, VJ increased his raw scores across years at the same rate as children from large standardisation samples, except for one task; he achieved average performance, consistent with his socio-educational background. He performed within normal range on 74% of recognition tests and achieved average to above average scores on 42% of them despite very severe impairment on 82% of episodic recall tasks. Both faces and landscapes-scenes gave rise to above average scores when tested with coloured stimuli. Cued recall, although impaired, was largely superior to free recall. This case supports a modular account of the MTL with episodic, but not semantic memory depending on the hippocampal formation. Furthermore, the overall pattern of findings is consistent with evidence from both brain-damaged and neuroimaging studies indicating that recollection requires intact hippocampal formation and familiarity relies, at least partly, on the adjacent temporal lobe cortex.

Real-time imaging of regional myocardial function using fast-SENC.

A technique for fast imaging of regional myocardial function using a spiral acquisition in combination with strain-encoded (SENC) magnetic resonance imaging (MRI) is presented in this paper. This technique, which is termed fast-SENC, enables scan durations as short as a single heartbeat. A reduced field of view (FOV) without foldover artifacts was achieved by localized SENC, which selectively excited the region around the heart. The two images required for SENC imaging (low- and high-tuning) were acquired in an interleaved fashion throughout the cardiac cycle to further shorten the scan time. Regional circumferential contraction and longitudinal shortening of both the left ventricle (LV) and right ventricle (RV) were examined in long- and short-axis views, respectively. The in vivo results obtained from five human subjects and five infarcted dogs are presented. The results of the fast-SENC technique in a single heartbeat acquisition were comparable to those obtained by conventional SENC in a long acquisition time. Therefore, fast-SENC may prove useful for imaging during stress or arrhythmia.

Simultaneous B(0)- and B(1)+-map acquisition for fast localized shim, frequency, and RF power determination in the heart at 3 T.

High-field (>or=3 T) cardiac MRI is challenged by inhomogeneities of both the static magnetic field (B(0)) and the transmit radiofrequency field (B(1)+). The inhomogeneous B fields not only demand improved shimming methods but also impede the correct determination of the zero-order terms, i.e., the local resonance frequency f(0) and the radiofrequency power to generate the intended local B(1)+ field. In this work, dual echo time B(0)-map and dual flip angle B(1)+-map acquisition methods are combined to acquire multislice B(0)- and B(1)+-maps simultaneously covering the entire heart in a single breath hold of 18 heartbeats. A previously proposed excitation pulse shape dependent slice profile correction is tested and applied to reduce systematic errors of the multislice B(1)+-map. Localized higher-order shim correction values including the zero-order terms for frequency f(0) and radiofrequency power can be determined based on the acquired B(0)- and B(1)+-maps. This method has been tested in 7 healthy adult human subjects at 3 T and improved the B(0) field homogeneity (standard deviation) from 60 Hz to 35 Hz and the average B(1)+ field from 77% to 100% of the desired B(1)+ field when compared to more commonly used preparation methods.

Navigator-gated free-breathing three-dimensional balanced fast field echo (TrueFISP) coronary magnetic resonance angiography.

RATIONALE AND OBJECTIVES: Recent developments of MR imaging equipment enabled high-quality steady state-free-precession (Balanced FFE, True-FISP) MR-imaging with a substantial 'T2 like' contrast, resulting in a high signal intensity of the blood-pool without the application of exogenous contrast agents. It is hypothesized that Balanced-FFE may be valuable for contrast enhancement in 3D free-breathing coronary MRA. MATERIALS AND METHODS: Navigator-gated free-breathing cardiac triggered coronary MRA was performed in 10 healthy adult subjects and three patients with radiograph defined coronary artery disease using a segmented k-space 3D Balanced FFE imaging sequence. RESULTS: High contrast-to-noise ratio between the blood-pool and the myocardium (29 +/- 8) and long segment visualization of both coronary arteries could be obtained in about 5 minutes during free breathing using the present navigator-gated Balanced-FFE coronary MRA approach. First patient results demonstrated successful display of coronary artery stenoses. CONCLUSION: Balanced FFE offers a potential alternative for endogenous contrast enhancement in navigator-gated free-breathing 3D coronary MRA. The obtained results together with the relatively short scanning time warrant further studies in larger patient collectives.

Compressed Sensing Single-Breath-Hold CMR for Fast Quantification of LV Function, Volumes, and Mass.

OBJECTIVES: The purpose of this study was to compare a novel compressed sensing (CS)-based single-breath-hold multislice magnetic resonance cine technique with the standard multi-breath-hold technique for the assessment of left ventricular (LV) volumes and function. BACKGROUND: Cardiac magnetic resonance is generally accepted as the gold standard for LV volume and function assessment. LV function is 1 of the most important cardiac parameters for diagnosis and the monitoring of treatment effects. Recently, CS techniques have emerged as a means to accelerate data acquisition. METHODS: The prototype CS cine sequence acquires 3 long-axis and 4 short-axis cine loops in 1 single breath-hold (temporal/spatial resolution: 30 ms/1.5 × 1.5 mm(2); acceleration factor 11.0) to measure left ventricular ejection fraction (LVEFCS) as well as LV volumes and LV mass using LV model-based 4D software. For comparison, a conventional stack of multi-breath-hold cine images was acquired (temporal/spatial resolution 40 ms/1.2 × 1.6 mm(2)). As a reference for the left ventricular stroke volume (LVSV), aortic flow was measured by phase-contrast acquisition. RESULTS: In 94% of the 33 participants (12 volunteers: mean age 33 ± 7 years; 21 patients: mean age 63 ± 13 years with different LV pathologies), the image quality of the CS acquisitions was excellent. LVEFCS and LVEFstandard were similar (48.5 ± 15.9% vs. 49.8 ± 15.8%; p = 0.11; r = 0.96; slope 0.97; p < 0.00001). Agreement of LVSVCS with aortic flow was superior to that of LVSVstandard (overestimation vs. aortic flow: 5.6 ± 6.5 ml vs. 16.2 ± 11.7 ml, respectively; p = 0.012) with less variability (r = 0.91; p < 0.00001 for the CS technique vs. r = 0.71; p < 0.01 for the standard technique). The intraobserver and interobserver agreement for all CS parameters was good (slopes 0.93 to 1.06; r = 0.90 to 0.99). CONCLUSIONS: The results demonstrated the feasibility of applying the CS strategy to evaluate LV function and volumes with high accuracy in patients. The single-breath-hold CS strategy has the potential to replace the multi-breath-hold standard cardiac magnetic resonance technique.