Electroencephalographic topography measures of experienced utility

Economic theory distinguishes two concepts of utility: decision utility, objectively quantifiable by choices, and experienced utility, referring to the satisfaction by an obtainment. To date, experienced utility is typically measured with subjective ratings. This study intended to quantify experienced utility by global levels of neuronal activity. Neuronal activity was measured by means of electroencephalographic (EEG) responses to gain and omission of graded monetary rewards at the level of the EEG topography in human subjects. A novel analysis approach allowed approximating psychophysiological value functions for the experienced utility of monetary rewards. In addition, we identified the time windows of the event-related potentials (ERP) and the respective intracortical sources, in which variations in neuronal activity were significantly related to the value or valence of outcomes. Results indicate that value functions of experienced utility and regret disproportionally increase with monetary value, and thus contradict the compressing value functions of decision utility. The temporal pattern of outcome evaluation suggests an initial (∼250 ms) coarse evaluation regarding the valence, concurrent with a finer-grained evaluation of the value of gained rewards, whereas the evaluation of the value of omitted rewards emerges later. We hypothesize that this temporal double dissociation is explained by reward prediction errors. Finally, a late, yet unreported, reward-sensitive ERP topography (∼500 ms) was identified. The sources of these topographical covariations are estimated in the ventromedial prefrontal cortex, the medial frontal gyrus, the anterior and posterior cingulate cortex and the hippocampus/amygdala. The results provide important new evidence regarding “how,” “when,” and “where” the brain evaluates outcomes with different hedonic impact.

Cohort study of trials submitted to ethics committee identified discrepant reporting of outcomes in publications

OBJECTIVES To identify factors associated with discrepant outcome reporting in randomized drug trials. STUDY DESIGN AND SETTING Cohort study of protocols submitted to a Swiss ethics committee 1988-1998: 227 protocols and amendments were compared with 333 matching articles published during 1990-2008. Discrepant reporting was defined as addition, omission, or reclassification of outcomes. RESULTS Overall, 870 of 2,966 unique outcomes were reported discrepantly (29.3%). Among protocol-defined primary outcomes, 6.9% were not reported (19 of 274), whereas 10.4% of reported outcomes (30 of 288) were not defined in the protocol. Corresponding percentages for secondary outcomes were 19.0% (284 of 1,495) and 14.1% (334 of 2,375). Discrepant reporting was more likely if P values were <0.05 compared with P ≥ 0.05 [adjusted odds ratio (aOR): 1.38; 95% confidence interval (CI): 1.07, 1.78], more likely for efficacy compared with harm outcomes (aOR: 2.99; 95% CI: 2.08, 4.30) and more likely for composite than for single outcomes (aOR: 1.48; 95% CI: 1.00, 2.20). Cardiology (aOR: 2.34; 95% CI: 1.44, 3.79) and infectious diseases (aOR: 1.77; 95% CI: 1.01, 3.13) had more discrepancies compared with all specialties combined. CONCLUSION Discrepant reporting was associated with statistical significance of results, type of outcome, and specialty area. Trial protocols should be made freely available, and the publications should describe and justify any changes made to protocol-defined outcomes.

Genetic testing for glucokinase mutations in clinically selected patients with MODY: a worthwhile investment

The differential diagnosis for children with diabetes includes a group of monogenic diabetic disorders known as maturity-onset diabetes of the young (MODY). So far, six underlying gene defects have been identified. The most common subtypes are caused by mutations in the genes encoding the transcription factor HNF-1a (MODY 3) and the glycolytic enzyme glucokinase (GCK) (MODY 2). MODY 2 is the most benign form of diabetes as the threshold for glucose sensing is elevated resulting in mild, regulated hyperglycemia. MODY 2 may usually be treated with diet alone without risk of microvascular complications. Patients with MODY usually present as children or young adults. Genetic testing for MODY in diabetic subjects is often not performed because of the costs and its unavailability in Switzerland. We describe the impact of the genetic analysis for MODY 2 on diabetes management and treatment costs in a five-year-old girl. The patient and her diabetic mother were both found to have a heterozygous missense mutation (V203A) in the glucokinase gene. The five-year-old girl was started on insulin therapy for her diabetes but because her HbA1c remained between 5.8-6.4% (reference 4.1-5.7%) and her clinical presentation suggested MODY insulin was discontinued. She is now well controlled on a carbohydrate controlled diet regimen only. Omission of insulin treatment made regular blood glucose monitoring unnecessary and removed her risk of hypoglycemia. Costs for the genetic analysis were 500 Euro. At our centre costs for diabetes care of a patient with type 1 diabetes are approximately 2050 Euro/year compared to 410 Euro/year for the care of a patient with MODY 2. In addition, a diagnosis of MODY 2 may reassure patients and their families, as microvascular complications are uncommon. Thus there are both health and financial benefits in diagnosing MODY 2. We recommend genetic testing for MODY 2 in clinically selected patients even though this analysis is currently not available in Switzerland and costs are not necessarily covered by the health insurances.

Impact of loading displacements on SLR-derived parameters and on the consistency between GNSS and SLR results

Displacements of the Earth’s surface caused by tidal and non-tidal loading forces are relevant in high-precision space geodesy. Some of the corrections are recommended by the international scientific community to be applied at the observation level, e.g., ocean tidal loading (OTL) and atmospheric tidal loading (ATL). Non-tidal displacement corrections are in general recommended not to be applied in the products of the International Earth Rotation and Reference Systems Service, in particular atmospheric non-tidal loading (ANTL), oceanic and hydrological non-tidal corrections. We assess and compare the impact of OTL, ATL and ANTL on SLR-derived parameters by reprocessing 12 years of SLR data considering and ignoring individual corrections. We show that loading displacements have an influence not only on station long-term stability, but also on geocenter coordinates, Earth Rotation Parameters, and satellite orbits. Applying the loading corrections reduces the amplitudes of annual signals in the time series of geocenter and station coordinates. The general improvement of the SLR station 3D coordinate repeatability when applying OTL, ATL and ANTL corrections are 19.5 %, 0.2 % and 3.3 % respectively, w.r.t. the solutions without loading corrections. ANTL corrections play a crucial role in the combination of optical (SLR) and microwave (GNSS, VLBI, DORIS) space geodetic observation techniques, because of the so-called Blue-Sky effect: SLR measurements can be carried out only under cloudless sky conditions—typically during high air pressure conditions, when the Earth’s crust is deformed, whereas microwave observations are weather-independent. Thus, applying the loading corrections at the observation level improves SLR-derived products as well as the consistency with microwave-based results. We assess the Blue-Sky effect on SLR stations and the consistency improvement between GNSS and SLR solutions when ANTL corrections are included. The omission of ANTL corrections may lead to inconsistencies between SLR and GNSS solutions of up to 2.5 mm for inland stations. As a result, the estimated GNSS–SLR coordinate differences correspond better to the local ties at the co-located stations when applying ANTL corrections.

A Prospective Multicenter SPOG 2003 FN Study of Microbiologically Defined Infections in Pediatric Cancer Patients with Fever and Neutropenia.

BACKGROUND Fever and neutropenia (FN) often complicate anticancer treatment and can be caused by potentially fatal infections. Knowledge of pathogen distribution is paramount for optimal patient management. METHODS Microbiologically defined infections (MDI) in pediatric cancer patients presenting with FN by nonmyeloablative chemotherapy enrolled in a prospective multi-center study were analyzed. Effectiveness of empiric antibiotic therapy in FN episodes with bacteremia was assessed taking into consideration recently published treatment guidelines for pediatric patients with FN. RESULTS MDI were identified in a minority (22%) of pediatric cancer patients with FN. In patients with, compared to without MDI, fever (median, 5 [IQR 3-8] vs. 2 [IQR1-3] days, p < 0.001) and hospitalization (10 [6-14] vs. 5 [3-8] days, p < 0.001) lasted longer, transfer to the intensive care unit was more likely (13 of 95 [14%] vs. 7 of 346 [2.0%], p < 0.001), and antibiotics were given longer (10 [7-14] vs. 5 [4-7], p < 0.001). Empiric antibiotic therapy in FN episodes with bacteremia was highly effective if not only intrinsic and reported antimicrobial susceptibilities were considered but the purposeful omission of coverage for coagulase negative staphylococci and enterococci was also taken into account (81% [95%CI 68 - 90] vs. 96.6% [95%CI 87 - 99.4], p = 0.004) CONCLUSIONS: MDI were identified in a minority of FN episodes but they significantly affected management and the clinical course of pediatric cancer patients. Compliance with published guidelines was associated with effectiveness of empiric antibiotic therapy in FN episodes with bacteremia.

"Is there a doctor on board?" - legal aspects of medical care in emergency situations during spare time

Medical emergencies on international flights are not uncommon. In these situations the question often arises whether physicians are obliged to render first aid and whether omission leads to legal consequences. The general obligation to aid those in need applies to everyone, not only to physicians. Evading this duty makes liable to prosecution for omittance of defence of a third person in line with Art. 128 of the Swiss Penal Code, punishable by custodial sentence up to three years or an equivalent punitive fine. Vocational and professional law extend the duty to aid for physicians to urgent cases. Although resulting from the performance of a legal obligation, malpractice occurred in the course of first aid can lead to claims for compensation - even from foreign patients, and that according to their own domestic law.

GRAIL gravity field determination using the Celestial Mechanics Approach

The NASA mission GRAIL (Gravity Recovery and Interior Laboratory) inherited its concept from the GRACE (Gravity Recovery and Climate Experiment) mission to determine the gravity field of the Moon. We present lunar gravity fields based on the data of GRAIL’s primary mission phase. Gravity field recovery is realized in the framework of the Celestial Mechanics Approach, using a development version of the Bernese GNSS Software along with Ka-band range-rate data series as observations and the GNI1B positions provided by NASA JPL as pseudo-observations. By comparing our results with the official level-2 GRAIL gravity field models we show that the lunar gravity field can be recovered with a high quality by adapting the Celestial Mechanics Approach, even when using pre-GRAIL gravity field models as a priori fields and when replacing sophisticated models of non-gravitational accelerations by appropriately spaced pseudo-stochastic pulses (i.e., instantaneous velocity changes). We present and evaluate two lunar gravity field solutions up to degree and order 200 – AIUB-GRL200A and AIUB-GRL200B. While the first solution uses no gravity field information beyond degree 200, the second is obtained by using the official GRAIL field GRGM900C up to degree and order 660 as a priori information. This reduces the omission errors and demonstrates the potential quality of our solution if we resolved the gravity field to higher degree.

Interaction of sulfate assimilation with carbon and nitrogen metabolism in Lemna minor

Cysteine synthesis from sulfide andO-acetyl-L-serine (OAS) is a reaction interconnecting sulfate, nitrogen, and carbon assimilation. UsingLemna minor, we analyzed the effects of omission of CO2 from the atmosphere and simultaneous application of alternative carbon sources on adenosine 5′-phosphosulfate reductase (APR) and nitrate reductase (NR), the key enzymes of sulfate and nitrate assimilation, respectively. Incubation in air without CO2 led to severe decrease in APR and NR activities and mRNA levels, but ribulose-1,5-bisphosphate carboxylase/oxygenase was not considerably affected. Simultaneous addition of sucrose (Suc) prevented the reduction in enzyme activities, but not in mRNA levels. OAS, a known regulator of sulfate assimilation, could also attenuate the effect of missing CO2 on APR, but did not affect NR. When the plants were subjected to normal air after a 24-h pretreatment in air without CO2, APR and NR activities and mRNA levels recovered within the next 24 h. The addition of Suc and glucose in air without CO2 also recovered both enzyme activities, with OAS again influenced only APR.35SO4 2− feeding showed that treatment in air without CO2 severely inhibited sulfate uptake and the flux through sulfate assimilation. After a resupply of normal air or the addition of Suc, incorporation of 35S into proteins and glutathione greatly increased. OAS treatment resulted in high labeling of cysteine; the incorporation of 35S in proteins and glutathione was much less increased compared with treatment with normal air or Suc. These results corroborate the tight interconnection of sulfate, nitrate, and carbon assimilation.

Outcome discrepancies and selective reporting: impacting the leading journals?

BACKGROUND Selective outcome reporting of either interesting or positive research findings is problematic, running the risk of poorly-informed treatment decisions. We aimed to assess the extent of outcome and other discrepancies and possible selective reporting between registry entries and published reports among leading medical journals. METHODS Randomized controlled trials published over a 6-month period from July to December 31st, 2013, were identified in five high impact medical journals: The Lancet, British Medical Journal, New England Journal of Medicine, Annals of Internal Medicine and Journal of American Medical Association were obtained. Discrepancies between published studies and registry entries were identified and related to factors including registration timing, source of funding and presence of statistically significant results. RESULTS Over the 6-month period, 137 RCTs were found. Of these, 18% (n = 25) had discrepancies related to primary outcomes with the primary outcome changed in 15% (n = 20). Moreover, differences relating to non-primary outcomes were found in 64% (n = 87) with both omission of pre-specified non-primary outcomes (39%) and introduction of new non-primary outcomes (44%) common. No relationship between primary or non-primary outcome change and registration timing (prospective or retrospective; P = 0.11), source of funding (P = 0.92) and presence of statistically significant results (P = 0.92) was found. CONCLUSIONS Discrepancies between registry entries and published articles for primary and non-primary outcomes were common among trials published in leading medical journals. Novel approaches are required to address this problem.

Regulation of Sulfate Assimilation by Nitrogen in Arabidopsis

Using Arabidopsis, we analyzed the effect of omission of a nitrogen source and of the addition of different nitrogen-containing compounds on the extractable activity and the enzyme and mRNA accumulation of adenosine 5′-phosphosulfate reductase (APR). During 72 h without a nitrogen source, the APR activity decreased to 70% and 50% of controls in leaves and roots, respectively, while cysteine (Cys) and glutathione contents were not affected. Northern and western analysis revealed that the decrease of APR activity was correlated with decreased mRNA and enzyme levels. The reduced APR activity in roots could be fully restored within 24 h by the addition of 4 mM each of NO3 −, NH4 +, or glutamine (Gln), or 1 mM O-acetylserine (OAS). 35SO4 2− feeding showed that after addition of NH4 +, Gln, or OAS to nitrogen-starved plants, incorporation of 35S into proteins significantly increased in roots; however, glutathione and Cys labeling was higher only with Gln and OAS or with OAS alone, respectively. OAS strongly increased mRNA levels of all three APR isoforms in roots and also those of sulfite reductase, Cys synthase, and serine acetyltransferase. Our data demonstrate that sulfate reduction is regulated by nitrogen nutrition at the transcriptional level and that OAS plays a major role in this regulation.

Molecular Characterization and Risk Factors of Giardia duodenalis among School Children from La Habana, Cuba

Giardia duodenalis is considered the most common protozoan infecting humans worldwide. Molecular characterization of G. duodenalis isolates has revealed the existence of eight groups (assemblages A to H) which differ in their host distribution. A cross-sectional study was conducted in 639 children from La Habana between January and December 2013. Two assemblage-specific PCRs were carried out for the molecular characterization. The overall prevalence of Giardia infection was 11.9%. DNA from 63 of 76 (82.9%) samples was successfully amplified by PCR-tpi, while 58 from 76 (76.3%) were detected by PCRE1-HF. Similar results by both PCRs were obtained in 54 from 76 samples (71%). According to these analyses, assemblage B and mixed assemblages A + B account for most of the Giardia infections in the cohort of children tested. Our current study identified assemblage B as predominant genotype in children infected with Giardia. Univariate analysis indicated that omission of washing hands before eating and keeping dogs at home were significant risk factors for a Giardia infection. In the future, novel molecular tools for a better discrimination of assemblages at the subassemblages level are needed to verify possible correlations between Giardia genotypes and symptomatology of giardiasis.

Polypharmacy and specific comorbidities in university primary care settings.

AIMS Polypharmacy is associated with adverse events and multimorbidity, but data are limited on its association with specific comorbidities in primary care settings. We measured the prevalence of polypharmacy and inappropriate prescribing, and assessed the association of polypharmacy with specific comorbidities. METHODS We did a cross-sectional analysis of 1002 patients aged 50-80years followed in Swiss university primary care settings. We defined polypharmacy as ≥5 long-term prescribed drugs and multimorbidity as ≥2 comorbidities. We used logistic mixed-effects regression to assess the association of polypharmacy with the number of comorbidities, multimorbidity, specific sets of comorbidities, potentially inappropriate prescribing (PIP) and potential prescribing omission (PPO). We used multilevel mixed-effects Poisson regression to assess the association of the number of drugs with the same parameters. RESULTS Patients (mean age 63.5years, 67.5% ≥2 comorbidities, 37.0% ≥5 drugs) had a mean of 3.9 (range 0-17) drugs. Age, BMI, multimorbidity, hypertension, diabetes mellitus, chronic kidney disease, and cardiovascular diseases were independently associated with polypharmacy. The association was particularly strong for hypertension (OR 8.49, 95%CI 5.25-13.73), multimorbidity (OR 6.14, 95%CI 4.16-9.08), and oldest age (75-80years: OR 4.73, 95%CI 2.46-9.10 vs.50-54years). The prevalence of PPO was 32.2% and PIP was more frequent among participants with polypharmacy (9.3% vs. 3.2%, p<0.006). CONCLUSIONS Polypharmacy is common in university primary care settings, is strongly associated with hypertension, diabetes mellitus, chronic kidney disease and cardiovascular diseases, and increases potentially inappropriate prescribing. Multimorbid patients should be included in further trials for developing adapted guidelines and avoiding inappropriate prescribing.