Guidelines for the clinical management of atrial fibrillation: a practical perspective.

Since the management of atrial fibrillation may be difficult in the individual patient, our purpose was to develop simple clinical recommendations to help the general internist manage this common clinical problem. Systematic review of the literature with evaluation of data-related evidence and framing of graded recommendations. Atrial fibrillation affects some 1% of the population in Western countries and is linked to a significant increase in morbidity and mortality. The management of atrial fibrillation requires individualised evaluation of the risks and benefits of therapeutic modalities, relying whenever possible on simple and validated tools. The two main points requiring a decision in clinical management are 1) whether or not to implement thromboembolic prevention therapy, and 2) whether preference should be given to a "rate control" or "rhythm control" strategy. Thromboembolic prophylaxis should be prescribed after individualised risk assessment: for patients at risk, oral anticoagulation with warfarin decreases the rate of embolic complications by 60% and aspirin by 20%, at the expense of an increased incidence of haemorrhagic complications. "Rate control" and "rhythm control" strategies are probably equivalent, and the choice should also be made on an individualised basis. To assist the physician in making his choices for the care of an atrial fibrillation patient we propose specific tables and algorithms, with graded recommendations. On the evidence of data from the literature we propose simple algorithms and tables for the clinical management of atrial fibrillation in the individual patient.

Magnetic resonance-guided, real-time targeted delivery and imaging of magnetocapsules immunoprotecting pancreatic islet cells.

In type I diabetes mellitus, islet transplantation provides a moment-to-moment fine regulation of insulin. Success rates vary widely, however, necessitating suitable methods to monitor islet delivery, engraftment and survival. Here magnetic resonance-trackable magnetocapsules have been used simultaneously to immunoprotect pancreatic beta-cells and to monitor, non-invasively in real-time, hepatic delivery and engraftment by magnetic resonance imaging (MRI). Magnetocapsules were detected as single capsules with an altered magnetic resonance appearance on capsule rupture. Magnetocapsules were functional in vivo because mouse beta-cells restored normal glycemia in streptozotocin-induced diabetic mice and human islets induced sustained C-peptide levels in swine. In this large-animal model, magnetocapsules could be precisely targeted for infusion by using magnetic resonance fluoroscopy, whereas MRI facilitated monitoring of liver engraftment over time. These findings are directly applicable to ongoing improvements in islet cell transplantation for human diabetes, particularly because our magnetocapsules comprise clinically applicable materials.

Quantitative Measurement of Brain Perfusion with Intravoxel Incoherent Motion MR Imaging.

Purpose: To evaluate the sensitivity of the perfusion parameters derived from Intravoxel Incoherent Motion (IVIM) MR imaging to hypercapnia-induced vasodilatation and hyperoxygenation-induced vasoconstriction in the human brain. Materials and Methods: This study was approved by the local ethics committee and informed consent was obtained from all participants. Images were acquired with a standard pulsed-gradient spin-echo sequence (Stejskal-Tanner) in a clinical 3-T system by using 16 b values ranging from 0 to 900 sec/mm(2). Seven healthy volunteers were examined while they inhaled four different gas mixtures known to modify brain perfusion (pure oxygen, ambient air, 5% CO(2) in ambient air, and 8% CO(2) in ambient air). Diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (f), and blood flow-related parameter (fD*) maps were calculated on the basis of the IVIM biexponential model, and the parametric maps were compared among the four different gas mixtures. Paired, one-tailed Student t tests were performed to assess for statistically significant differences. Results: Signal decay curves were biexponential in the brain parenchyma of all volunteers. When compared with inhaled ambient air, the IVIM perfusion parameters D*, f, and fD* increased as the concentration of inhaled CO(2) was increased (for the entire brain, P = .01 for f, D*, and fD* for CO(2) 5%; P = .02 for f, and P = .01 for D* and fD* for CO(2) 8%), and a trend toward a reduction was observed when participants inhaled pure oxygen (although P > .05). D remained globally stable. Conclusion: The IVIM perfusion parameters were reactive to hyperoxygenation-induced vasoconstriction and hypercapnia-induced vasodilatation. Accordingly, IVIM imaging was found to be a valid and promising method to quantify brain perfusion in humans. © RSNA, 2012.

A forensic perspective of the AFL investigation into peptides: an antidoping investigation case study.

BACKGROUND: The World Anti-Doping Agency (WADA) is introducing enhancements to doping investigations in its 2015 Code, which include improved sharing of information between antidoping organisations (including sporting bodies) and enhanced accountability of athlete support staff. These additions will improve the control of links between sports doping and organised crime. In February 2013 the Australian Crime Commission released a report that linked several professional sporting codes, professional athletes with links to organised crime, performance enhancing drugs and illicit substances. Following this report the Australian Football League (AFL) partnered the Australian national antidoping organisation to investigate peptide use in Australian football. METHODS: This review compared the model proposed by Marclay, a hypothetical model for anti-doping investigations that proposed a forensic intelligence and analysis approach, to use the forensic capabilities of the AFL investigation to test the model's relevance to an actual case. RESULTS: The investigation uncovered the use of peptides used to enhance athlete performance. The AFL investigation found a high risk of doping where athlete support staff existed in teams with weak corporate governance controls. A further finding included the need for the investigation to provide a timely response in professional team sports that were sensitive to the competition timing. In the case of the AFL the team was sanctioned prior to the finals as an interim outcome for allowing the risk of use of performance-enhancing substances. Doping violation charges are still being considered. DISCUSSION: Antidoping strategies should include the investigation of corporate officers in team doping circumstances, the mandatory recording of all athlete substance use during competition and training phases, the wider sharing of forensic intelligence with non-sporting bodies particularly law enforcement and collaboration between antidoping and sporting organisations in doping investigations. CONCLUSIONS: The AFL investigation illustrated the importance of the 2015 WADA Code changes and highlighted the need for a systematic use of broad forensic intelligence activities in the investigation of doping violations.

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.

Simulating the Impact of Sectorial Productivity Gains on Two Regional Economies: Key Sectors from a Supply Side Perspective

In this paper we simulate and analyse the economic impact that sectorial productivity gains have on two regional Spanish economies (Catalonia and Extremadura). In particular we study the quantitative effect that each sector’s productivity gain has on household welfare (real disposable income and equivalent variation), on the consumption price indices and factor relative prices, on real production (GDP) and on the government’s net income (net taxation revenues of social transfers to households). The analytical approach consists of a computable general equilibrium model, in which we assume perfect competition and cleared markets, including factor markets. All the parameters and exogenous variables of the model are calibrated by means of two social accounting matrices, one for each region under study. The results allow us to identify those sectors with the greatest impact on consumer welfare as the key sectors in the regional economies. Keywords: Productivity gains, key sectors, computable general equilibrium

Noninvasive imaging of 5-HT3 receptor trafficking in live cells: from biosynthesis to endocytosis.

Sequential stages in the life cycle of the ionotropic 5-HT(3) receptor (5-HT(3)R) were resolved temporally and spatially in live cells by multicolor fluorescence confocal microscopy. The insertion of the enhanced cyan fluorescent protein into the large intracellular loop delivered a fluorescent 5-HT(3)R fully functional in terms of ligand binding specificity and channel activity, which allowed for the first time a complete real-time visualization and documentation of intracellular biogenesis, membrane targeting, and ligand-mediated internalization of a receptor belonging to the ligand-gated ion channel superfamily. Fluorescence signals of newly expressed receptors were detectable in the endoplasmic reticulum about 3 h after transfection onset. At this stage receptor subunits assembled to form active ligand binding sites as demonstrated in situ by binding of a fluorescent 5-HT(3)R-specific antagonist. After novel protein synthesis was chemically blocked, the 5-HT(3) R populations in the endoplasmic reticulum and Golgi cisternae moved virtually quantitatively to the cell surface, indicating efficient receptor folding and assembly. Intracellular 5-HT(3) receptors were trafficking in vesicle-like structures along microtubules to the cell surface at a velocity generally below 1 mum/s and were inserted into the plasma membrane in a characteristic cluster distribution overlapping with actin-rich domains. Internalization of cell surface 5-HT(3) receptors was observed within minutes after exposure to an extracellular agonist. Our orchestrated use of spectrally distinguishable fluorescent labels for the receptor, its cognate ligand, and specific organelle markers can be regarded as a general approach allowing subcellular insights into dynamic processes of membrane receptor trafficking.

Noninvasive detection of macrophage-rich atherosclerotic plaque in hyperlipidemic rabbits using "positive contrast" magnetic resonance imaging.

OBJECTIVES: This study was designed to identify macrophage-rich atherosclerotic plaque noninvasively by imaging the tissue uptake of long-circulating superparamagnetic nanoparticles with a positive contrast off-resonance imaging sequence (inversion recovery with ON-resonant water suppression [IRON]). BACKGROUND: The sudden rupture of macrophage-rich atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary vessels, resulting in acute myocardial infarction. Therefore, a noninvasive technique that can identify macrophage-rich plaques and thereby assist with risk stratification of patients with atherosclerosis would be of great potential clinical utility. METHODS: Experiments were conducted on a clinical 3-T magnetic resonance imaging (MRI) scanner in 7 heritable hyperlipidemic and 4 control rabbits. Monocrystalline iron-oxide nanoparticles (MION)-47 were administrated intravenously (2 doses of 250 mumol Fe/kg), and animals underwent serial IRON-MRI before injection of the nanoparticles and serially after 1, 3, and 6 days. RESULTS: After administration of MION-47, a striking signal enhancement was found in areas of plaque only in hyperlipidemic rabbits. The magnitude of enhancement on magnetic resonance images had a high correlation with the number of macrophages determined by histology (p < 0.001) and allowed for the detection of macrophage-rich plaque with high accuracy (area under the curve: 0.92, SE: 0.04, 95% confidence interval: 0.84 to 0.96, p < 0.001). No significant signal enhancement was measured in remote areas without plaque by histology and in control rabbits without atherosclerosis. CONCLUSIONS: Using IRON-MRI in conjunction with superparamagnetic nanoparticles is a promising approach for the noninvasive evaluation of macrophage-rich, vulnerable plaques.

Length of hospital stay and postdischarge mortality in patients with pulmonary embolism: a statewide perspective

BACKGROUND: The optimal length of stay (LOS) for patients with pulmonary embolism (PE) is unknown. Although reducing LOS is likely to save costs, the effects on patient safety are unclear. We sought to identify patient and hospital factors associated with LOS and assess whether LOS was associated with postdischarge mortality. METHODS: We evaluated patients discharged with a primary diagnosis of PE from 186 acute care hospitals in Pennsylvania (January 2000 through November 2002). We used discrete survival models to examine the association between (1) patient and hospital factors and the time to discharge and (2) LOS and postdischarge mortality within 30 days of presentation, adjusting for patient and hospital factors. RESULTS: Among 15 531 patient discharges with PE, the median LOS was 6 days, and postdischarge mortality rate was 3.3%. In multivariate analysis, patients from Philadelphia were less likely to be discharged on a given day (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.73-0.93), as were black patients (OR, 0.88; 95% CI, 0.82-0.94).The odds of discharge decreased notably with greater patient severity of illness and in patients without private health insurance. Adjusted postdischarge mortality was significantly higher for patients with an LOS of 4 days or less (OR, 1.55; 95% CI, 1.21-2.00) relative to those with an LOS of 5 to 6 days. CONCLUSIONS: Several hospital and patient factors were independently associated with LOS. Patients with a very short LOS had greater postdischarge mortality relative to patients with a typical LOS, suggesting that physicians may inappropriately select patients with PE for early discharge who are at increased risk of complications

An interactive perspective of health education for the tropical disease control: the schistosomiasis case

Some municipalities in Brazil have been requesting orientation for the implementation of health education programs related to the control of schistosomiasis. This demand was based on experiences in the development of health education researches, strategies and materials for school-age children, involving the communities and secretaries of health and education. Motivated by this request and the recently implemented plan of health services (Unified Health System - Sistema Único de Saúde - SUS) that gives autonomy to the municipalities to utilize health resources and services in Brazil, this paper presents an interactive perspective of planning health education research and programs. The purpose of this perspective is to stimulate a reflection on the needs and actions of institutions and people involved in health education research and/or programs to obtain sustainability, commitment and effectiveness - not only in the control of schistosomiasis, but also in the improvement of environmental conditions, quality of life and personal health. This perspective comprises interaction among three levels related to health education programs: the decision level, the executive level and the beneficiary level. The needs and lines of action at each of these levels are discussed, as well as the ways in which they can interact with each other. This proposal may lead to useful interactive ways of planing, organizing, executing and evaluating health education research and/or program, not only towards the prevention and control of the disease at stake, but also to promote health in general.