Somewhere between illusion of control and powerlessness : trying to situate the pathological gambler's locus of control

It has been suggested that pathological gamblers develop illusory perceptions of control regarding the outcome of the games and should express higher Internal and Chance locus of control. A sample of 48 outpatients diagnosed with pathological gambling disorder who participated in this ex post facto study, completed the Internality, Powerful Others, and Chance scale, the South Oaks Gambling Screen questionnaire, and the Beck Depression Inventory. Results for the locus of control measure were compared with a reference group. Pathological gamblers scored higher than the reference group on the Chance locus of control, which increased with the severity of cases. Moreover, Internal locus of control did show a curvilinear relationship with the severity of cases. Pathological gamblers have specific locus of control scores that vary in function of the severity, in a linear fashion or a non-linear fashion according to the scale. This effect might be caused by competition between "illusion of control" and the tendency to attribute adverse consequence of gambling to external causes.

Cardiorenal end points in a trial of aliskiren for type 2 diabetes.

BACKGROUND: This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS: In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS: The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P=0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, ≥6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P<0.001 for both comparisons). CONCLUSIONS: The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.).

Impact of preoperative embolization of the left gastric artery on the rate of anastomotic leakage after esophageal resection

Objective: Impaired blood flow of the gastric tube represents a major cause of anastomotic leakage after esophageal resection. In order to improve local vascularisation, preoperative embolization (PE) of the left gastric artery has recently been proposed. The aimof this study was to assess our initial experience of this novel approach with a particular focus on anastomotic leakage.Methods: A consecutive series of 102 patients (81 male, 21 female, median age 64 years) underwent resection (82 Ivor-Lewis procedures, 9 transhiatal resections, 11 triple incisions) for esophageal malignancies at our institution from 2000 to 2009. Since 2004, PE was used selectively in 19 patients 21 days prior to elective esophagectomy. Selection criteria were normal gastric vascular anatomy, no pre-existing vascular disease, i.e. atheromatosis of the celiac trunk or superior mesenteric artery, and resectability of the tumor. PE was performed under local anesthesia on a dedicated system in a standard fashion. Following percutaneous transfemoral visceral angiography to identify gastric vascular anatomy, embolization was performed either with 5-F or with coaxial 3-F catheters and fibered metal coils. We analyzed retrospectively patient's data, operative data, and outcome from a prospective database.Results: The overall anastomotic leakage rate was 18・6% (19/102 patients); cervical anastomosis had a leak rate of 25% compared to intrathoracic anastomosis leak rate of 18・2%. While 17 of 83 patients without PE developed anastomotic leakage (20・5%), there were only 2 of 19 patients after PE revealing an anastomotic leakage (10・5%). Otherwise, patients with PE had no more other complications. There was only one PE-related complication (i.e. partial splenic necrosis).Mean hospital stay was 25 days versus 27 days for patients with PE and without PE, respectively. The mortality rate was 7・8% (8/102 patients), whereby four deaths were related to anastomotic leakage (1 and 3 patients with PE and without PE, respectively).Conclusion: PE is an interesting novel approach to improve gastric blood flow in order to minimize anastomotic leakage. Its application is safe and technically easy. Our preliminary experience revealed a decrease of the anastomotic leakage rate of almost 50%.

Ligamentous and tendinous anatomy of the intermetacarpal and common carpometacarpal joints: evaluation with MR imaging and MR arthrography.

PURPOSE: The purpose of this work was to demonstrate the normal ligamentous and tendinous anatomy of the intermetacarpal (IMC) and common carpometacarpal (CCMC) joints with MRI and MR arthrography. METHOD: MR images of 22 wrists derived from fresh human cadavers were obtained before and after arthrography. The MR imaging features of the ligaments and tendons about the CCMC and IMC joints and the joints themselves were analyzed in a randomized fashion and correlated with those seen on anatomic sections. RESULTS: Six CCMC ligaments were visualized. The dorsal and palmar CCMC ligaments and the pisometacarpal ligament were best visualized in the sagittal plane. The radial and ulnar CCMC collateral ligaments and the capito-third metacarpal ligament were best visualized in the coronal plane. Three main IMC ligaments were observed: a dorsal and a palmar ligament and an interosseous ligament complex. All three ligaments were best visualized in the axial plane. Four tendinous insertions to the metacarpal bases were evident. CONCLUSION: The anatomy of the ligaments and tendinous insertions about the second to fifth IMC and the CCMC joints is well demonstrated by MR imaging and MR arthrography. MR arthrography does not significantly improve the visualization of these complex structures.

Dose-dependent effect of atrial natriuretic peptide on blood pressure, heart rate, and skin blood flow of normal volunteers.

Synthetic atrial natriuretic peptide, containing 26 amino acids in the rat sequence, L-364, 343 (Ileu-ANP), was infused intravenously at increasing rates (1-40 micrograms/min) into four normal volunteers. Mean intraarterial blood pressure decreased and heart rate increased in cumulative-dose-dependent fashion. Skin blood flow as measured with a laser Doppler device rose already with a cumulative dose of 55 micrograms Ileu-ANP and further rises were directly related to dose. The only side effects observed were those accompanying symptomatic hypotension at higher doses. These findings provide strong evidence that Ileu-ANP acts as a vasodilator in normal volunteers.

Defining the level of evidence for technology adoption in the localized prostate cancer pathway.

New technologies in prostate cancer are attempting to change the current prostate cancer pathway by aiming to reduce harms while maintaining the benefits associated with screening, diagnosis, and treatment. In this article, we discuss the optimal evaluation that new technologies should undergo to provide level 1 evidence typically required to change the practice. With this in mind, we focus on feasible and pragmatic trials that could be delivered in a timely fashion by many centers while retaining primary outcomes that focus on clinically meaningful outcomes.

Effect of n-3 fatty acids on cerebral markers and the inflammatory response in sepsis

Introduction ICM+ software encapsulates our 20 years' experience in brain monitoring. It collects data from a variety of bedside monitors and produces time trends of parameters defi ned using confi gurable mathematical formulae. To date it is being used in nearly 40 clinical research centres worldwide. We present its application for continuous monitoring of cerebral autoregulation using near-infrared spectroscopy (NIRS). Methods Data from multiple bedside monitors are processed by ICM+ in real time using a large selection of signal processing methods. These include various time and frequency domain analysis functions as well as fully customisable digital fi lters. The fi nal results are displayed in a variety of ways including simple time trends, as well as time window based histograms, cross histograms, correlations, and so forth. All this allows complex information from bedside monitors to be summarized in a concise fashion and presented to medical and nursing staff in a simple way that alerts them to the development of various pathological processes. Results One hundred and fi fty patients monitored continuously with NIRS, arterial blood pressure (ABP) and intracranial pressure (ICP), where available, were included in this study. There were 40 severely headinjured adult patients, 27 SAH patients (NCCU, Cambridge); 60 patients undergoing cardiopulmonary bypass (John Hopkins Hospital, Baltimore) and 23 patients with sepsis (University Hospital, Basel). In addition, MCA fl ow velocity (FV) was monitored intermittently using transcranial Doppler. FV-derived and ICP-derived pressure reactivity indices (PRx, Mx), as well as NIRS-derived reactivity indices (Cox, Tox, Thx) were calculated and showed signifi cant correlation with each other in all cohorts. Errorbar charts showing reactivity index PRx versus CPP (optimal CPP chart) as well as similar curves for NIRS indices versus CPP and ABP were also demonstrated. Conclusions ICM+ software is proving to be a very useful tool for enhancing the battery of available means for monitoring cerebral vasoreactivity and potentially facilitating autoregulation guided therapy. Complexity of data analysis is also hidden inside loadable profi les, thus allowing investigators to take full advantage of validated protocols including advanced processing formulas.

Clinical pharmacology of atrial natriuretic (3-28) eicosahexapeptide.

The clinical pharmacology of a synthetic rat atrial natriuretic peptide (rANP) was evaluated in normal volunteers. During a dose-ranging study at 1-40 micrograms/min we observed a dose-dependent decrease in mean intra-arterial blood pressure, an acceleration of the heart rate and a transient increase in blood flow to the skin. During a 4-h constant-dose infusion at 0.5 and 5.0 micrograms/min, inulin clearance remained unchanged but there was a dose-related fall in paraaminohippurate (PAH) clearance and an increase in the filtration fraction. Urinary excretion of sodium, chloride and calcium increased in a dose-related fashion, but with the high dose the excretion curve had a bell-shape. No change in plasma renin activity, angiotensin II and aldosterone was observed during the rANP infusion despite the excretion of large amounts of sodium and a blood pressure reduction with the high dose. Indocyanine green clearance, a measure of hepatic blood flow, was significantly decreased by a 2-h rANP infusion at 1.0 microgram/min. In normal volunteers, therefore, rANP induced vasodilation and blood pressure reduction, a decrease in renal and hepatic blood flow and a natriuretic and transient diuretic effect without activation of the renin-angiotensin-aldosterone system.

Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis.

BACKGROUND: Interleukin-1 is pivotal in the pathogenesis of systemic juvenile idiopathic arthritis (JIA). We assessed the efficacy and safety of canakinumab, a selective, fully human, anti-interleukin-1β monoclonal antibody, in two trials. METHODS: In trial 1, we randomly assigned patients, 2 to 19 years of age, with systemic JIA and active systemic features (fever; ≥2 active joints; C-reactive protein, >30 mg per liter; and glucocorticoid dose, ≤1.0 mg per kilogram of body weight per day), in a double-blind fashion, to a single subcutaneous dose of canakinumab (4 mg per kilogram) or placebo. The primary outcome, termed adapted JIA ACR 30 response, was defined as improvement of 30% or more in at least three of the six core criteria for JIA, worsening of more than 30% in no more than one of the criteria, and resolution of fever. In trial 2, after 32 weeks of open-label treatment with canakinumab, patients who had a response and underwent glucocorticoid tapering were randomly assigned to continued treatment with canakinumab or to placebo. The primary outcome was time to flare of systemic JIA. RESULTS: At day 15 in trial 1, more patients in the canakinumab group had an adapted JIA ACR 30 response (36 of 43 [84%], vs. 4 of 41 [10%] in the placebo group; P<0.001). In trial 2, among the 100 patients (of 177 in the open-label phase) who underwent randomization in the withdrawal phase, the risk of flare was lower among patients who continued to receive canakinumab than among those who were switched to placebo (74% of patients in the canakinumab group had no flare, vs. 25% in the placebo group, according to Kaplan-Meier estimates; hazard ratio, 0.36; P=0.003). The average glucocorticoid dose was reduced from 0.34 to 0.05 mg per kilogram per day, and glucocorticoids were discontinued in 42 of 128 patients (33%). The macrophage activation syndrome occurred in 7 patients; infections were more frequent with canakinumab than with placebo. CONCLUSIONS: These two phase 3 studies show the efficacy of canakinumab in systemic JIA with active systemic features. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT00889863 and NCT00886769.).

Learning wind fields with multiple kernels

This paper presents multiple kernel learning (MKL) regression as an exploratory spatial data analysis and modelling tool. The MKL approach is introduced as an extension of support vector regression, where MKL uses dedicated kernels to divide a given task into sub-problems and to treat them separately in an effective way. It provides better interpretability to non-linear robust kernel regression at the cost of a more complex numerical optimization. In particular, we investigate the use of MKL as a tool that allows us to avoid using ad-hoc topographic indices as covariables in statistical models in complex terrains. Instead, MKL learns these relationships from the data in a non-parametric fashion. A study on data simulated from real terrain features confirms the ability of MKL to enhance the interpretability of data-driven models and to aid feature selection without degrading predictive performances. Here we examine the stability of the MKL algorithm with respect to the number of training data samples and to the presence of noise. The results of a real case study are also presented, where MKL is able to exploit a large set of terrain features computed at multiple spatial scales, when predicting mean wind speed in an Alpine region.

Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis.

BACKGROUND: Interleukin-1 is pivotal in the pathogenesis of systemic juvenile idiopathic arthritis (JIA). We assessed the efficacy and safety of canakinumab, a selective, fully human, anti-interleukin-1β monoclonal antibody, in two trials. METHODS: In trial 1, we randomly assigned patients, 2 to 19 years of age, with systemic JIA and active systemic features (fever; ≥2 active joints; C-reactive protein, >30 mg per liter; and glucocorticoid dose, ≤1.0 mg per kilogram of body weight per day), in a double-blind fashion, to a single subcutaneous dose of canakinumab (4 mg per kilogram) or placebo. The primary outcome, termed adapted JIA ACR 30 response, was defined as improvement of 30% or more in at least three of the six core criteria for JIA, worsening of more than 30% in no more than one of the criteria, and resolution of fever. In trial 2, after 32 weeks of open-label treatment with canakinumab, patients who had a response and underwent glucocorticoid tapering were randomly assigned to continued treatment with canakinumab or to placebo. The primary outcome was time to flare of systemic JIA. RESULTS: At day 15 in trial 1, more patients in the canakinumab group had an adapted JIA ACR 30 response (36 of 43 [84%], vs. 4 of 41 [10%] in the placebo group; P<0.001). In trial 2, among the 100 patients (of 177 in the open-label phase) who underwent randomization in the withdrawal phase, the risk of flare was lower among patients who continued to receive canakinumab than among those who were switched to placebo (74% of patients in the canakinumab group had no flare, vs. 25% in the placebo group, according to Kaplan-Meier estimates; hazard ratio, 0.36; P=0.003). The average glucocorticoid dose was reduced from 0.34 to 0.05 mg per kilogram per day, and glucocorticoids were discontinued in 42 of 128 patients (33%). The macrophage activation syndrome occurred in 7 patients; infections were more frequent with canakinumab than with placebo. CONCLUSIONS: These two phase 3 studies show the efficacy of canakinumab in systemic JIA with active systemic features. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT00889863 and NCT00886769.).

The views of rich Europeans are more likely to be reflected by political parties than those of poorer citizens

How does income inequality affect political representation? Jan Rosset, Nathalie Giger and Julian Bernauer examine whether politicians represent the views of poorer and richer citizens equally. They find that in 43 out of the 49 elections included in their analysis, the preferences of low-income citizens are located further away from the policy positions of the closest political party than those with mid-range incomes. This suggests that income inequality may spill-over into political inequalities, although it is less clear whether this effect is likely to get better or worse as a result of the Eurozone crisis.

Normal pathogen-specific immune responses mounted by CTLA-4-deficient T cells: a paradigm reconsidered.

CTLA-4 is a critical negative regulator of T cell responses and CTLA-4-deficient (CTLA-4(-/-)) mice die of a lymphproliferative disease. Nevertheless, RAG-2-deficient mice reconstituted with a mixture of CTLA-4(-/-) and normal (CTLA-4(+/+)) bone marrow survive in the absence of any signs of disease, although 50% of their T cells do not express CTLA-4. Using such mixed chimeras, we analyzed the role of CTLA-4 in specific T cell responses to lymphocytic choriomeningitis virus, Leishmania major and mouse mammary tumor virus, which cause acute, chronic and persistent infections, respectively. The populations of antigen-specific CTLA-4(-/-)CD4(+) and CTLA-4(-/-)CD8(+) T cells became activated, expanded and contracted indistinguishably from CTLA-4(+/+)CD4(+) and CTLA-4(+/+)CD8(+) T cells after infection with all three pathogens. Thus, CTLA-4 is not involved in the down-regulation of specific T cell responses and peripheral deletion in a T cell-autonomous fashion.

Calcium entry blockade attenuates the acute blood pressure rise induced by cigarette smoking.

The purpose of this study was to assess whether the administration of a calcium entry blocker can prevent the acute blood pressure rise induced by cigarette smoking. Seven male habitual smokers were included. After 45 min of equilibration, they took in randomized single-blind fashion at a 1 week interval either a placebo or nifedipine, 10 mg p.o. Thirty minutes thereafter, the subjects smoked within 10 min two cigarettes containing 1.4 mg of nicotine each. In addition to heart rate and skin blood flow (laser Doppler method), blood pressure of the median left finger was monitored continuously for 100 min using a noninvasive device (Finapres). Nifedipine induced an increase in skin blood flow that was not influenced by smoking. This skin blood flow response was observed although nifedipine had by itself no effect on systemic blood pressure. The calcium antagonist markedly attenuated the blood pressure rise induced by cigarette smoking. However, it tended to accentuate the heart rate acceleration resulting from inhalation of nicotine-containing smoke.

PKCθ/β and CYLD are antagonistic partners in the NFκB and NFAT transactivation pathways in primary mouse CD3+ T lymphocytes.

In T cells PKCθ mediates the activation of critical signals downstream of TCR/CD28 stimulation. We investigated the molecular mechanisms by which PKCθ regulates NFκB transactivation by examining PKCθ/β single and double knockout mice and observed a redundant involvement of PKCθ and PKCβ in this signaling pathway. Mechanistically, we define a PKCθ-CYLD protein complex and an interaction between the positive PKCθ/β and the negative CYLD signaling pathways that both converge at the level of TAK1/IKK/I-κBα/NFκB and NFAT transactivation. In Jurkat leukemic T cells, CYLD is endoproteolytically processed in the initial minutes of stimulation by the paracaspase MALT1 in a PKC-dependent fashion, which is required for robust IL-2 transcription. However, in primary T cells, CYLD processing occurs with different kinetics and an altered dependence on PKC. The formation of a direct PKCθ/CYLD complex appears to regulate the short-term spatial distribution of CYLD, subsequently affecting NFκB and NFAT repressional activity of CYLD prior to its MALT1-dependent inactivation. Taken together, our study establishes CYLD as a new and critical PKCθ interactor in T cells and reveals that antagonistic PKCθ/β-CYLD crosstalk is crucial for the adjustment of immune thresholds in primary mouse CD3(+) T cells.