Monitoring the Time Course of Perception without Awareness: A Comparison of Mirror Masked Words and Nonwords

Mirror masked words are embedded into a context that makes them appear as senseless patterns or as strings of unfamiliar letters. Thus, mirror masked words can be shown for several hundreds of milliseconds without being recognised as words. We sought to further investigate effects of nonsconscious reading by monitoring event-related brain potentials (ERPs) while participants observed mirror masked letter strings. ERPs were recorded while participants observed mirror masked words and nonwords. Data of 15 participants was segmented into periods of quasi-stable field topography (microstates). Microstates for masked words and nonwords were compared using randomization tests, statistical parametric scalp maps and Low Resolution Electromagnetic Tomography (LORETA). ERPs to masked words and nonwords showed significant topographic differences between 136 and 256 ms, indicating that stimuli were nonconsciously discriminated. A LORETA model localised sources of activation discriminating between masked words and nonwords in left operculum, the right superior parietal lobe and right superior temporal gyrus indicating higher current density for nonwords than for words in these areas. ERPs of mirror masked stimuli can indicate unconscious discrimination even in cases where behavioural priming is unreliable. This approach might be useful for investigating differences in early, nonconscious stages of word perception.

Interventions for the management of mandibular fractures

BACKGROUND Fractures of the mandible (lower jaw) are a common occurrence and usually related to interpersonal violence or road traffic accidents. Mandibular fractures may be treated using open (surgical) and closed (non-surgical) techniques. Fracture sites are immobilized with intermaxillary fixation (IMF) or other external or internal devices (i.e. plates and screws) to allow bone healing. Various techniques have been used, however uncertainty exists with respect to the specific indications for each approach. OBJECTIVES The objective of this review is to provide reliable evidence of the effects of any interventions either open (surgical) or closed (non-surgical) that can be used in the management of mandibular fractures, excluding the condyles, in adult patients. SEARCH METHODS We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 28 February 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 1), MEDLINE via OVID (1950 to 28 February 2013), EMBASE via OVID (1980 to 28 February 2013), metaRegister of Controlled Trials (to 7 April 2013), ClinicalTrials.gov (to 7 April 2013) and the WHO International Clinical Trials Registry Platform (to 7 April 2013). The reference lists of all trials identified were checked for further studies. There were no restrictions regarding language or date of publication. SELECTION CRITERIA Randomised controlled trials evaluating the management of mandibular fractures without condylar involvement. Any studies that compared different treatment approaches were included. DATA COLLECTION AND ANALYSIS At least two review authors independently assessed trial quality and extracted data. Results were to be expressed as random-effects models using mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals. Heterogeneity was to be investigated to include both clinical and methodological factors. MAIN RESULTS Twelve studies, assessed as high (six) and unclear (six) risk of bias, comprising 689 participants (830 fractures), were included. Interventions examined different plate materials and morphology; use of one or two lag screws; microplate versus miniplate; early and delayed mobilization; eyelet wires versus Rapid IMF™ and the management of angle fractures with intraoral access alone or combined with a transbuccal approach. Patient-oriented outcomes were largely ignored and post-operative pain scores were inadequately reported. Unfortunately, only one or two trials with small sample sizes were conducted for each comparison and outcome. Our results and conclusions should therefore be interpreted with caution. We were able to pool the results for two comparisons assessing one outcome. Pooled data from two studies comparing two miniplates versus one miniplate revealed no significant difference in the risk of post-operative infection of surgical site (risk ratio (RR) 1.32, 95% CI 0.41 to 4.22, P = 0.64, I(2) = 0%). Similarly, no difference in post-operative infection between the use of two 3-dimensional (3D) and standard (2D) miniplates was determined (RR 1.26, 95% CI 0.19 to 8.13, P = 0.81, I(2) = 27%). The included studies involved a small number of participants with a low number of events. AUTHORS' CONCLUSIONS This review illustrates that there is currently inadequate evidence to support the effectiveness of a single approach in the management of mandibular fractures without condylar involvement. The lack of high quality evidence may be explained by clinical diversity, variability in assessment tools used and difficulty in grading outcomes with existing measurement tools. Until high level evidence is available, treatment decisions should continue to be based on the clinician's prior experience and the individual circumstances.

Chronic NSAID use and long-term decline of renal function in a prospective rheumatoid arthritis cohort study

OBJECTIVES Non-steroidal anti-inflammatory drugs (NSAIDs) may cause kidney damage. This study assessed the impact of prolonged NSAID exposure on renal function in a large rheumatoid arthritis (RA) patient cohort. METHODS Renal function was prospectively followed between 1996 and 2007 in 4101 RA patients with multilevel mixed models for longitudinal data over a mean period of 3.2 years. Among the 2739 'NSAID users' were 1290 patients treated with cyclooxygenase type 2 selective NSAIDs, while 1362 subjects were 'NSAID naive'. Primary outcome was the estimated glomerular filtration rate according to the Cockroft-Gault formula (eGFRCG), and secondary the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration formula equations and serum creatinine concentrations. In sensitivity analyses, NSAID dosing effects were compared for patients with NSAID registration in ≤/>50%, ≤/>80% or ≤/>90% of assessments. FINDINGS In patients with baseline eGFRCG >30 mL/min, eGFRCG evolved without significant differences over time between 'NSAID users' (mean change in eGFRCG -0.87 mL/min/year, 95% CI -1.15 to -0.59) and 'NSAID naive' (-0.67 mL/min/year, 95% CI -1.26 to -0.09, p=0.63). In a multivariate Cox regression analysis adjusted for significant confounders age, sex, body mass index, arterial hypertension, heart disease and for other insignificant factors, NSAIDs were an independent predictor for accelerated renal function decline only in patients with advanced baseline renal impairment (eGFRCG <30 mL/min). Analyses with secondary outcomes and sensitivity analyses confirmed these results. CONCLUSIONS NSAIDs had no negative impact on renal function estimates but in patients with advanced renal impairment.

Adherence as a Predictor of the Development of Class-Specific Resistance Mutations: The Swiss HIV Cohort Study

Background Non-adherence is one of the strongest predictors of therapeutic failure in HIV-positive patients. Virologic failure with subsequent emergence of resistance reduces future treatment options and long-term clinical success. Methods Prospective observational cohort study including patients starting new class of antiretroviral therapy (ART) between 2003 and 2010. Participants were naïve to ART class and completed ≥1 adherence questionnaire prior to resistance testing. Outcomes were development of any IAS-USA, class-specific, or M184V mutations. Associations between adherence and resistance were estimated using logistic regression models stratified by ART class. Results Of 314 included individuals, 162 started NNRTI and 152 a PI/r regimen. Adherence was similar between groups with 85% reporting adherence ≥95%. Number of new mutations increased with increasing non-adherence. In NNRTI group, multivariable models indicated a significant linear association in odds of developing IAS-USA (odds ratio (OR) 1.66, 95% confidence interval (CI): 1.04-2.67) or class-specific (OR 1.65, 95% CI: 1.00-2.70) mutations. Levels of drug resistance were considerably lower in PI/r group and adherence was only significantly associated with M184V mutations (OR 8.38, 95% CI: 1.26-55.70). Adherence was significantly associated with HIV RNA in PI/r but not NNRTI regimens. Conclusion Therapies containing PI/r appear more forgiving to incomplete adherence compared with NNRTI regimens, which allow higher levels of resistance, even with adherence above 95%. However, in failing PI/r regimens good adherence may prevent accumulation of further resistance mutations and therefore help to preserve future drug options. In contrast, adherence levels have little impact on NNRTI treatments once the first mutations have emerged.

White blood cell count and mortality in patients with acute pulmonary embolism

Although associated with adverse outcomes in other cardiovascular diseases, the prognostic value of an elevated white blood cell (WBC) count, a marker of inflammation and hypercoagulability, is uncertain in patients with pulmonary embolism (PE). We therefore sought to assess the prognostic impact of the WBC in a large, state-wide retrospective cohort of patients with PE. We evaluated 14,228 patient discharges with a primary diagnosis of PE from 186 hospitals in Pennsylvania. We used random-intercept logistic regression to assess the independent association between WBC count levels at the time of presentation and mortality and hospital readmission within 30 days, adjusting for patient and hospital characteristics. Patients with an admission WBC count <5.0, 5.0-7.8, 7.9-9.8, 9.9-12.6, and >12.6 × 10(9) /L had a cumulative 30-day mortality of 10.9%, 6.2%, 5.4%, 8.3%, and 16.3% (P < 0.001), and a readmission rate of 17.6%, 11.9%, 10.9%, 11.5%, and 15.0%, respectively (P < 0.001). Compared with patients with a WBC count 7.9-9.8 × 10(9) /L, adjusted odds of 30-day mortality were significantly greater for patients with a WBC count <5.0 × 10(9) /L (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.14-2.03), 9.9-12.6 × 10(9) /L (OR 1.55, 95% CI 1.26-1.91), or >12.6 × 10(9) /L (OR 2.22, 95% CI 1.83-2.69), respectively. The adjusted odds of readmission were also significantly increased for patients with a WBC count <5.0 × 10(9) /L (OR 1.34, 95% CI 1.07-1.68) or >12.6 × 10(9) /L (OR 1.29, 95% CI 1.10-1.51). In patients presenting with PE, WBC count is an independent predictor of short-term mortality and hospital readmission.

Optimizing the size of the area surveyed for monitoring a Eurasian lynx (Lynx lynx) population in the Swiss Alps by means of photographic capture-recapture

We studied the influence of surveyed area size on density estimates by means of camera-trapping in a low-density felid population (1-2 individuals/100 km(2) ). We applied non-spatial capture-recapture (CR) and spatial CR (SCR) models for Eurasian lynx during winter 2005/2006 in the northwestern Swiss Alps by sampling an area divided into 5 nested plots ranging from 65 to 760 km(2) . CR model density estimates (95% CI) for models M0 and Mh decreased from 2.61 (1.55-3.68) and 3.6 (1.62-5.57) independent lynx/100 km(2) , respectively, in the smallest to 1.20 (1.04-1.35) and 1.26 (0.89-1.63) independent lynx/100 km(2) , respectively, in the largest area surveyed. SCR model density estimates also decreased with increasing sampling area but not significantly. High individual range overlaps in relatively small areas (the edge effect) is the most plausible reason for this positive bias in the CR models. Our results confirm that SCR models are much more robust to changes in trap array size than CR models, thus avoiding overestimation of density in smaller areas. However, when a study is concerned with monitoring population changes, large spatial efforts (area surveyed ≥760 km(2) ) are required to obtain reliable and precise density estimates with these population densities and recapture rates.

Safety of non-therapeutic atomoxetine exposures - a national poison data system study

AIMS This study's objective is to assess the safety of non-therapeutic atomoxetine exposures reported to the US National Poison Database System (NPDS). METHODS This is a retrospective database study of non-therapeutic single agent ingestions of atomoxetine in children and adults reported to the NPDS between 2002 and 2010. RESULTS A total of 20 032 atomoxetine exposures were reported during the study period, and 12 370 of these were single agent exposures. The median age was 9 years (interquartile range 3, 14), and 7380 were male (59.7%). Of the single agent exposures, 8813 (71.2%) were acute exposures, 3315 (26.8%) were acute-on-chronic, and 166 (1.3%) were chronic. In 10 608 (85.8%) cases, exposure was unintentional, in 1079 (8.7%) suicide attempts, and in 629 (5.1%) cases abuse. Of these cases, 3633 (29.4 %) were managed at health-care facilities. Acute-on-chronic exposure was associated with an increased risk of a suicidal reason for exposure compared with acute ingestions (odds ratio 1.44, 95% confidence interval 1.26-1.65). Most common clinical effects were drowsiness or lethargy (709 cases; 5.7%), tachycardia (555; 4.5%), and nausea (388; 3.1%). Major toxicity was observed in 21 cases (seizures in nine (42.9%), tachycardia in eight (38.1%), coma in six (28.6%), and ventricular dysrhythmia in one case (4.8%)). CONCLUSIONS Non-therapeutic atomoxetine exposures were largely safe, but seizures were rarely observed.

Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial

IMPORTANCE International guidelines advocate a 7- to 14-day course of systemic glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease (COPD). However, the optimal dose and duration are unknown. OBJECTIVE To investigate whether a short-term (5 days) systemic glucocorticoid treatment in patients with COPD exacerbation is noninferior to conventional (14 days) treatment in clinical outcome and whether it decreases the exposure to steroids. DESIGN, SETTING, AND PATIENTS REDUCE: (Reduction in the Use of Corticosteroids in Exacerbated COPD), a randomized, noninferiority multicenter trial in 5 Swiss teaching hospitals, enrolling 314 patients presenting to the emergency department with acute COPD exacerbation, past or present smokers (≥20 pack-years) without a history of asthma, from March 2006 through February 2011. INTERVENTIONS Treatment with 40 mg of prednisone daily for either 5 or 14 days in a placebo-controlled, double-blind fashion. The predefined noninferiority criterion was an absolute increase in exacerbations of at most 15%, translating to a critical hazard ratio of 1.515 for a reference event rate of 50%. MAIN OUTCOME AND MEASURE Time to next exacerbation within 180 days. RESULTS Of 314 randomized patients, 289 (92%) of whom were admitted to the hospital, 311 were included in the intention-to-treat analysis and 296 in the per-protocol analysis. Hazard ratios for the short-term vs conventional treatment group were 0.95 (90% CI, 0.70 to 1.29; P = .006 for noninferiority) in the intention-to-treat analysis and 0.93 (90% CI, 0.68 to 1.26; P = .005 for noninferiority) in the per-protocol analysis, meeting our noninferiority criterion. In the short-term group, 56 patients (35.9%) reached the primary end point; 57 (36.8%) in the conventional group. Estimates of reexacerbation rates within 180 days were 37.2% (95% CI, 29.5% to 44.9%) in the short-term; 38.4% (95% CI, 30.6% to 46.3%) in the conventional, with a difference of -1.2% (95% CI, -12.2% to 9.8%) between the short-term and the conventional. Among patients with a reexacerbation, the median time to event was 43.5 days (interquartile range [IQR], 13 to 118) in the short-term and 29 days (IQR, 16 to 85) in the conventional. There was no difference between groups in time to death, the combined end point of exacerbation, death, or both and recovery of lung function. In the conventional group, mean cumulative prednisone dose was significantly higher (793 mg [95% CI, 710 to 876 mg] vs 379 mg [95% CI, 311 to 446 mg], P < .001), but treatment-associated adverse reactions, including hyperglycemia and hypertension, did not occur more frequently. CONCLUSIONS AND RELEVANCE In patients presenting to the emergency department with acute exacerbations of COPD, 5-day treatment with systemic glucocorticoids was noninferior to 14-day treatment with regard to reexacerbation within 6 months of follow-up but significantly reduced glucocorticoid exposure. These findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN19646069.

Las redes académicas de Albrecht von Haller y la Sociedad Económica: un análisis de redes a varios niveles

En este artículo se ofrece un análisis de redes a varios niveles a través del ejemplo de la transferencia de plantas cultivadas dentro del contexto de las redes de correspondencia de Albrecht von Haller y la Sociedad Económica. Por medio de un procedimiento a varios niveles se analizan, una a una, la dinámica cronológica, la estructura social, la distribución espacial y la creación funcional de redes. Estos cuatro niveles de análisis de redes no están en conflicto unos con otros, sino que se complementan mutuamente. El objetivo consiste en comprender mejor cómo contribuyeron dichas redes a la transferencia internacional de conocimientos en el siglo XVIII. Palabras clave: República de las Letras, Ilustración Económica, Transferencia de plantas útiles

Persistent Deadlock in Multilateral Trade Negotiations: The Case of Doha

The history of the General Agreement on Tariffs and Trade negotiations is full of anecdotes on missed deadlines, failed ministerial conferences, and brinkmanship situations. Tactics such as walking away from the table or sleep-depriving night sessions are legendary in the context of attempting to overcome impasse in negotiations. This article traces and explains the recurrent deadlock in the Doha Round negotiations. It identifies four structural/contextual factors – ideas, institutions, interests, and information – as necessary for understanding and anticipating potential deadlocks. The article also offers a definition of deadlock, and discusses a set of factors highlighted in the international relations literature that explain the existence and persistence of deadlock. With the help of game theory, it then illustrates the challenges faced by actors during trade negotiations. The article concludes by outlining two general scenarios for the Doha Development Agenda and discusses their implications for the World Trade Organization.

Total IgE and allergen-specific IgE and IgG antibody levels in sera of atopic dermatitis affected and non-affected Labrador- and Golden retrievers.

Canine atopic dermatitis (CAD) is an allergic skin disease associated with IgE and IgG antibodies (Ab) to environmental allergens. The aim of this study was to determine which other factors influence serum Ab levels in CAD-affected and non-affected dogs as this has only been poorly investigated in dogs so far. Total and allergen-specific IgE levels and Dermatophagoides farinae (DF)-specific IgG1 and IgG4 were measured by ELISA in sera of 145 CAD-affected and 271 non-affected Labrador- and Golden retrievers. A multivariable logistic regression analysis including the factors age, breed, gender, castration, clinical CAD status and allergen-specific immunotherapy (ASIT) was performed. Golden retrievers had more frequently total (OR=1.87, 95% CI=1.26-2.87, p<0.01) and specific IgE levels above the threshold value than Labrador retrievers, suggesting that genetic factors influence IgE levels in dogs. Castration was generally associated with low Ab levels (OR=0.43-0.65, p<0.05). Surprisingly, dogs with CAD did not have increased odds for high IgE against any of the allergens tested. ASIT with DF was associated with high DF-specific IgG1 (OR=4.32, 95% CI 1.46-12.8, p<0.01) but was not associated with DF-specific IgG4 or decreased IgE levels. Further studies are needed to understand the role of allergen-specific IgE in CAD and of IgG1 in ASIT.

Extent and distribution of calcification of both the aortic annulus and the left ventricular outflow tract predict aortic regurgitation after transcatheter aortic valve replacement

Aims: We sought to analyse local distribution of aortic annulus and left ventricular outflow tract (LVOT) calcification in patients undergoing transcatheter aortic valve replacement (TAVR) and its impact on aortic regurgitation (AR) immediately after device placement. Methods and results: A group of 177 patients with severe aortic stenosis undergoing multislice computed tomography of the aortic root followed by TAVR were enrolled in this single-centre study. Annular and LVOT calcifications were assessed per cusp using a semi-quantitative grading system (0: none; 1 [mild]: small, non-protruding calcifications; 2 [moderate]: protruding [>1 mm] or extensive [>50% of cusp sector] calcifications; 3 [severe]: protruding and extensive calcifications). Any calcification of the annulus or LVOT was present in 107 (61%) and 63 (36%) patients, respectively. Prevalence of annulus/LVOT calcifications in the left coronary cusp was 42% and 25%, respectively, in the non-coronary cusp 28% and 13%, in the right coronary cusp 13% and 5%. AR grade 2 to 4 assessed by the method of Sellers immediately after TAVR device implantation was observed in 55 patients (31%). Multivariate regression analysis revealed that the overall annulus calcification (OR [95% CI] 1.48 [1.10-2.00]; p=0.0106), the overall LVOT calcification (1.93 [1.26-2.96]; p=0.0026), any moderate or severe LVOT calcification (5.37 [1.52-18.99]; p=0.0092), and asymmetric LVOT calcification were independent predictors of AR. Conclusions: Calcifications of the aortic annulus and LVOT are frequent in patients undergoing TAVR, and both the distribution and the severity of calcifications appear to be independent predictors of aortic regurgitation after device implantation. - See more at: http://www.pcronline.com/eurointervention/77th_issue/126/#sthash.Hzodgju5.dpuf