Initial experiences with in vivo right coronary artery human MR vessel wall imaging at 3 tesla.

Due to their relatively small size and central location within the thorax, improvement in signal-to-noise (SNR) is of paramount importance for in vivo coronary vessel wall imaging. Thus, with higher field strengths, coronary vessel wall imaging is likely to benefit from the expected "near linear" proportional gain in SNR. In this study, we demonstrate the feasibility of in vivo human high field (3 T) coronary vessel wall imaging using a free-breathing black blood fast gradient echo technique with respiratory navigator gating and real-time motion correction. With the broader availability of more SNR efficient fast spin echo and spiral techniques, further improvements can be expected.

A century of global equity market correlations

In this paper, we use a unique long-run dataset of regulatory constraints on capital account openness to explain stock market correlations. Since stock returns themselves are highly volatile, any examination of what drives correlations needs to focus on long runs of data. This is particularly true since some of the short-term changes in co-movements appear to reverse themselves (Delroy Hunter 2005). We argue that changes in the co-movement of indices have not been random. Rather, they are mainly driven by greater freedom to move funds from one country to another. In related work, Geert Bekaert and Campbell Harvey (2000) show that equity correlations increase after liberalization of capital markets, using a number of case studies from emerging countries. We examine this pattern systematically for the last century, and find it to be most pronounced in the recent past. We compare the importance of capital account openness with one main alternative explanation, the growing synchronization of economic fundamentals. We conclude that greater openness has been the single most important cause of growing correlations during the last quarter of a century, though increasingly correlated economic fundamentals also matter. In the conclusion, we offer some thoughts on why the effects of greater openness appear to be so much stronger today than they were during the last era of globalization before 1914.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

OBJECTIVE: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock," published in 2004. DESIGN: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. METHODS: We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. RESULTS: Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). CONCLUSION: There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

Physiologically based pharmacokinetic modeling of arsenic in the mouse

A remarkable feature of the carcinogenicity of inorganic arsenic is that while human exposures to high concentrations of inorganic arsenic in drinking water are associated with increases in skin, lung, and bladder cancer, inorganic arsenic has not typically caused tumors in standard laboratory animal test protocols. Inorganic arsenic administered for periods of up to 2 yr to various strains of laboratory mice, including the Swiss CD-1, Swiss CR:NIH(S), C57Bl/6p53(+/-), and C57Bl/6p53(+/+), has not resulted in significant increases in tumor incidence. However, Ng et al. (1999) have reported a 40% tumor incidence in C57Bl/6J mice exposed to arsenic in their drinking water throughout their lifetime, with no tumors reported in controls. In order to investigate the potential role of tissue dosimetry in differential susceptibility to arsenic carcinogenicity, a physiologically based pharmacokinetic (PBPK) model for inorganic arsenic in the rat, hamster, monkey, and human (Mann et al., 1996a, 1996b) was extended to describe the kinetics in the mouse. The PBPK model was parameterized in the mouse using published data from acute exposures of B6C3F1 mice to arsenate, arsenite, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) and validated using data from acute exposures of C57Black mice. Predictions of the acute model were then compared with data from chronic exposures. There was no evidence of changes in the apparent volume of distribution or in the tissue-plasma concentration ratios between acute and chronic exposure that might support the possibility of inducible arsenite efflux. The PBPK model was also used to project tissue dosimetry in the C57Bl/6J study, in comparison with tissue levels in studies having shorter duration but higher arsenic treatment concentrations. The model evaluation indicates that pharmacokinetic factors do not provide an explanation for the difference in outcomes across the various mouse bioassays. Other possible explanations may relate to strain-specific differences, or to the different durations of dosing in each of the mouse studies, given the evidence that inorganic arsenic is likely to be active in the later stages of the carcinogenic process. [Authors]

Vers un accès à des soins de qualité pour les personnes lesbiennes, gays, bisexuelles et transgenres. [Access to quality primary care for LGBT people].

Cet article propose une approche globale de la santé des personnes lesbiennes, gays, bisexuelles, et transgenres (LGBT), où respect des singularités et non-jugement occupent une position centrale. Il invite à dépasser une vision centrée sur les risques liés au VIH. Pour qui n'a pas connu de questionnement en lien avec son orientation sexuelle ou son identité de genre, il est difficile de concevoir comment la découverte d'une caractéristique identitaire pendant l'enfance peut se transformer sous le regard des autres en un fardeau souvent invisible mais fréquemment associé avec une morbidité émotionnelle et médicale considérable. Cet article pose la question suivante : combien de personnes LGBT ressortent chaque semaine d'une consultation médicale sans avoir eu l'opportunité de bénéficier d'une écoute, d'un soutien et de soins adaptés ? [Abstract] This article offers a comprehensive approach to the health of lesbian, gay, bisexual and transgender (LGBT) people, where respect for diversity and non judgemental care play a central role. It calls for a health and medical vision that goes beyond HIV risk. For those who never had to question their own sexual orientation or gender identity, it is certainly difficult to understand how the discovery of one's identity trait in childhood or early adolescence can be transformed under social pressure into a burden which often remains invisible but is associated with considerable emotional and medical morbidity. This article raises the following question : How many LGBT patients go unnoticed every week, leaving the physician's office without an opportunity to receive appropriate listening, support and care ?

Inclusive fitness theory and eusociality.

Arising from M. A. Nowak, C. E. Tarnita & E. O. Wilson 466, 1057-1062 (2010); Nowak et al. reply. Nowak et al. argue that inclusive fitness theory has been of little value in explaining the natural world, and that it has led to negligible progress in explaining the evolution of eusociality. However, we believe that their arguments are based upon a misunderstanding of evolutionary theory and a misrepresentation of the empirical literature. We will focus our comments on three general issues.

A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes

Ras proteins are small guanosine triphosphatases involved in the regulation of important cellular functions such as proliferation, differentiation, and apoptosis. Understanding the intracellular trafficking of Ras proteins is crucial to identify novel Ras signaling platforms. In this study, we report that epidermal growth factor triggers Kirsten Ras (KRas) translocation onto endosomal membranes (independently of calmodulin and protein kinase C phosphorylation) through a clathrin-dependent pathway. From early endosomes, KRas but not Harvey Ras or neuroblastoma Ras is sorted and transported to late endosomes (LEs) and lysosomes. Using yellow fluorescent protein¿Raf1 and the Raichu-KRas probe, we identified for the first time in vivo¿active KRas on Rab7 LEs, eliciting a signal output through Raf1. On these LEs, we also identified the p14¿MP1 scaffolding complex and activated extracellular signal-regulated kinase 1/2. Abrogation of lysosomal function leads to a sustained late endosomal mitogen-activated protein kinase signal output. Altogether, this study reveals novel aspects about KRas intracellular trafficking and signaling, shedding new light on the mechanisms controlling Ras regulation in the cell.

Clinical experience with adalimumab in a multicenter Swiss cohort of patients with Crohn's disease.

BACKGROUND: Controlled clinical trials have demonstrated the efficacy and safety of adalimumab in patients with moderate-to-severe Crohn's disease (CD), but there is, however, only limited long-term experience with adalimumab in daily practice. AIM: To assess the long-term effectiveness and safety of adalimumab in a multicenter cohort of practice-based patients with moderate-to-severe CD. METHODS: We retrospectively reviewed the charts of CD patients who received adalimumab over a 3-year period. Disease severity was scored using the Harvey-Bradshaw index (HBI). Remission was defined as an HBI of <or=4 and response as a reduction in the HBI of >3 points at evaluation compared to the baseline. Univariate logistic regression analysis was used to identify the predictive variables associated with response. RESULTS: The charts of 55 patients were reviewed; remission and response rates observed at weeks 4-6 were 52.7 and 83.6%, respectively. Remission was maintained at weeks 12, 24 and 52 in 89.6, 72.4 and 44.7% of patients, respectively. Remission and response rates were not influenced by smoking status, disease location or duration, the first month total dose, or previous infliximab therapy. The remission rate at weeks 4-6 was significantly higher in patients intolerant of infliximab as compared to those who lost response to this drug. Adalimumab was well tolerated overall. CONCLUSION: Adalimumab can be considered a suitable option in patients with moderate-to-severe CD, demonstrating sustained long-term effectiveness.

AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushing's syndrome.

Chronic exposure to glucocorticoid hormones, resulting from either drug treatment or Cushing's syndrome, results in insulin resistance, central obesity, and symptoms similar to the metabolic syndrome. We hypothesized that the major metabolic effects of corticosteroids are mediated by changes in the key metabolic enzyme adenosine monophosphate-activated protein kinase (AMPK) activity. Activation of AMPK is known to stimulate appetite in the hypothalamus and stimulate catabolic processes in the periphery. We assessed AMPK activity and the expression of several metabolic enzymes in the hypothalamus, liver, adipose tissue, and heart of a rat glucocorticoid-excess model as well as in in vitro studies using primary human adipose and primary rat hypothalamic cell cultures, and a human hepatoma cell line treated with dexamethasone and metformin. Glucocorticoid treatment inhibited AMPK activity in rat adipose tissue and heart, while stimulating it in the liver and hypothalamus. Similar data were observed in vitro in the primary adipose and hypothalamic cells and in the liver cell line. Metformin, a known AMPK regulator, prevented the corticosteroid-induced effects on AMPK in human adipocytes and rat hypothalamic neurons. Our data suggest that glucocorticoid-induced changes in AMPK constitute a novel mechanism that could explain the increase in appetite, the deposition of lipids in visceral adipose and hepatic tissue, as well as the cardiac changes that are all characteristic of glucocorticoid excess. Our data suggest that metformin treatment could be effective in preventing the metabolic complications of chronic glucocorticoid excess.

"Maurice" de James Ivory . ¿Traïció a la Tradició Clàssica en adaptar la novel·la d'E. M. Forster?

D'acord amb els estudis sobre literatura i cinema i des del punt de vista de la influència de la Tradició Clàssica -Tradició Grega Clàssica, en aquest cas-, aquest article és una anàlisi acurada de les traïcions inevitables -fins a un cert punt- dels guionistes respecte dels textos literaris que adapten. Tanmateix, malgrat ser pràcticament inevitable, el Dr. Pau Gilabert Barberà indica quins són en opinió seva els límits que Ivory/Hesketh-Harvey no haurien d'haver ultrapassat a fir de no diluir el temperament hel·lènic de "Maurice" d'E. M. Forster.

"Maurice" de James Ivory . ¿Traición a la Tradición Clásica al adaptar la novela de E. M. Forster?

De acuerdo con los estudios sobre literatura y cine y desde el punto de vista de la influencia de la Tradición Clásica -Tradición Griega Clásica, en este caso-, este artículo es un análisis minucioso de las traiciones inevitables ¿hasta un cierto punto- de los guionistas a los textos literarios que adaptan. Sin embargo, a pesar de ser prácticamente inevitable, el Dr. Pau Gilabert Barberà indica cuáles son en su opinión los límites más allá de los cuales Ivory/Hesketh-Harvey no deberían haber ido a fin de no diluir el temperamento helénico de "Maurice" de E. M. Forster.

Was the Classical Tradition Betrayed by J. Ivory's adaptation of E. M. Forster's "Maurice"?

According to Literature and Film studies and from the point of view of the influence of Classical Tradition on Western Culture -Classical Greek Tradition, in this case-, this article is an accurate analysis of the inevitable -to a certain degree- screenwriters betrayals regarding the literary texts that they adapt. However, in spite of being practically inevitable, Dr. Pau Gilabert Barberà indicates which are in his opinion the limits beyond which Ivory/Hesketh-Harvey should have not gone in order not to dilute the Hellenic temper of E. M. Forster's Maurice.

Generalized Weyl solutions

It was shown by Weyl that the general static axisymmetric solution of the vacuum Einstein equations in four dimensions is given in terms of a single axisymmetric solution of the Laplace equation in three-dimensional flat space. Weyls construction is generalized here to arbitrary dimension D>~4. The general solution of the D-dimensional vacuum Einstein equations that admits D-2 orthogonal commuting non-null Killing vector fields is given either in terms of D-3 independent axisymmetric solutions of Laplaces equation in three-dimensional flat space or by D-4 independent solutions of Laplaces equation in two-dimensional flat space. Explicit examples of new solutions are given. These include a five-dimensional asymptotically flat black ring with an event horizon of topology S1S2 held in equilibrium by a conical singularity in the form of a disk.

Supersymmetric black rings and three-charge supertubes

We present supergravity solutions for 1/8-supersymmetric black supertubes with three charges and three dipoles. Their reduction to five dimensions yields supersymmetric black rings with regular horizons and two independent angular momenta. The general solution contains seven independent parameters and provides the first example of nonuniqueness of supersymmetric black holes. In ten dimensions, the solutions can be realized as D1-D5-P black supertubes. We also present a worldvolume construction of a supertube that exhibits three dipoles explicitly. This description allows an arbitrary cross section but captures only one of the angular momenta.