Neural correlates of adaptive cognitive control in working memory.

Conflicts in working memory (WM) can occur when retrieval cues activate competing items, which impairs the efficiency of retrieval. It has recently been shown that WM retrieval adapts similarly to these conflicts as predicted by conflict monitoring theory for selective attention tasks. Here, we utilized event-related potentials (ERPs) to investigate whether conflict and adaptive control in WM are reflected by the same neural markers that have previously been described for selective attention tasks. In our task, participants encoded two differently colored memory lists that contained four digits each (i.e., 2 5 7 1 and 4 5 9 1), and had to recognize whether a probe item from a specific list and position was correct or incorrect. Conflict during retrieval emerged when digits at corresponding positions (e.g., 2 and 5 at the first position) were different (incongruent), but not when these digits were the same (congruent). In behavioral data, we found a congruency sequence effect, that is, responses to incongruent probe items were slower, and this effect was reduced following trials with incongruent probe items. In ERPs, this behavioral marker of adaptive control was accompanied by two effects. First, congruency affected the amplitude of an N450, and this conflict effect was reduced after incongruent trials. Second, the posterior P3 amplitude varied with the congruency of the current and the previous trial. Both results resemble those found for the Stroop task and thus highlight the similarity between conflict and adaptive control in WM and selective attention tasks.

Adaptive control of working memory.

The present study investigated mechanisms of adaptive cognitive control in working memory (WM). WM is conceived as a system for short-term maintenance, updating and manipulation of representations required for goal-directed action. Adaptive control refers to the finding of flexible adjustments of control processes based on conflict. For instance, a higher frequency of incongruent stimuli, that is, stimuli evoking conflicting response tendencies, leads to a higher level of cognitive control as reflected by smaller congruency effects (i.e., the difference between congruent and incongruent items). Likewise, conflict on the previous trial leads to a higher level of cognitive control on the current trial. To investigate adaptive control in WM, we used a modified Sternberg paradigm. Participants memorized two differently colored lists of four digits (i.e., 2 5 7 1), in which corresponding positions in both lists contained the same digits (congruent items) or different digits (incongruent items). Participants were required to make a match/mismatch judgement (Experiment 1 and 2) or to recollect the correct digit at a probed position in one of the two lists (Experiment 3). In all experiments, we could replicate both hallmark effects of adaptive control, the proportion congruency effect, and the congruency sequence effect. Our results strongly support the assumption that WM representations can be dynamically adapted based on the amount of conflict, and that adaptive control of WM follows the same principles that have previously been shown for selective attention.

Sustainability of effects and secondary long-term outcomes: One-year follow-up of a cluster-randomized controlled trial to prevent maltreatment in institutional care.

BACKGROUND: Many orphans in East Africa are living in institutional care facilities where they experience poor quality of care and ongoing maltreatment. We report on the extension of a cluster-randomized controlled trial aiming to replicate and show sustainability of previous found effects and to discover long-term effects of the intervention Interaction Competencies with Children-for Caregivers (ICC-C) 12-months after the intervention's conclusion. METHODS: Conducting a robust 2x3 analysis of variance, we investigated the changes over time in the waitlist orphanages (n = 75, 62.7% female, Mage = 37.63 years, SDage = 11.81), which participated in the intervention after first follow-up and in the initial intervention orphanages (n = 81, 61.7% female, Mage = 38.73 years, SDage = 11.94). RESULTS: The caregivers in the waitlist orphanages reported less reported levels of maltreatment (d = -0.09), fewer positive attitudes towards violent discipline (d = -0.44) and increased childcare knowledge (d = 1.26) three months after intervention, replicating our findings of the initial intervention condition. In addition, these effects were maintained in the intervention orphanages 12 months post intervention. Furthermore, we found long-term improvements in negative caregiver-child relationship (d = -0.83), caregivers' stress level (d = -0.98) and their mental health problems (d = -0.61). CONCLUSIONS: The replication and maintenance of the intervention effects and first hints to additional long-term effects substantiates the effectiveness of ICC-C. As long as alternative care cannot be provided for all children in need, brief caregiver trainings can make an important contribution to enlarge the opportunities for many children. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03594617. Registered on 20 July 2018.

Same same but different? Modeling N-1 switch cost and N-2 repetition cost with the diffusion model and the linear ballistic accumulator model.

In three task-switching experiments, we investigated the relationship of n-1 switch cost and n-2 repetition cost. N-1 switch cost is observed when participants are asked to switch from one classification task to another, e.g., from judging a digit as odd or even to judging a digit as smaller or larger than five. N-2 repetition cost is observed when participants are asked to switch among three tasks (thereafter called A, B, and C). This cost is observed when the task on trial n-2 is repeated in trial n (i.e., in task sequences like ABA) compared to when it is switched (i.e., in task sequences like CBA). So far, the n-1 switch cost is assumed to be caused either by reconfiguration processes or by episodic-memory inertia from the previously activated task-set. N-2 repetition cost is thought to reflect lingering inhibitory processes for resolving conflict among tasks. Whereas both views are integrated in some models, it is up to date unclear whether n-2 repetition cost is related to n-1 switch cost. To examine this relationship, we decomposed the processes underlying n-1 switch cost and n-2 repetition cost using a diffusion model analysis as well as a linear ballistic accumulator model. The results showed that n-1 switch cost reflects interference caused by the residual activation of the previous task set as indicated by slower evidence accumulation processes. In contrast, there were no consistent parameter modulations underlying n-2 repetition cost. These findings emphasize that different cognitive processes are involved in n-1 switch cost and n-2 repetition cost.

Characterization and quantification of Sm(III)/ and Cm(III)/clay mineral outer-sphere species by TRLFS in D2O and EXAFS studies.

In order to assess the long-term safety of deep radioactive waste repositories, a precise characterization of the different sorption processes on a molecular basis and the exact definition of geochemical boundary conditions for their relevance are of immense importance. Through sorption on various minerals the migration of radionuclides will be hindered and their retention will be ensured. Using time-resolved laser fluorescence spectroscopy (TRLFS) and extended X-ray absorption fine structure (EXAFS) spectroscopy, it was possible to identify outer-sphere sorbed trivalent lanthanides and actinides onto different montmorillonites and illite. Furthermore, the quantification of Cm(III)/clay outer-sphere sorption in D(2)O at different ionic strengths was shown. The results were confirmed by ion exchange model calculations. Finally, the structural parameters of a Sm(III)/clay outer-sphere complex were obtained by EXAFS measurements.

Excretion of 2,3-dihydroxy-propionamide (OH-PA), the hydrolysis product of glycidamide, in human urine after single oral dose of deuterium-labeled acrylamide.

A dose of 0.99 mg d(3)-acrylamide (d(3)-AA) (13.2 µg/kg body weight) was ingested by a healthy male volunteer. Urine samples were collected over a period of 46 h after the intake and analyzed for the hydrolysis product of glycidamide (GA), 2,3-dihydroxy-propionamide (OH-PA), a metabolite of the toxicologically relevant oxidative AA metabolism pathway; 5.4% of the administered d(3)-AA dose was eliminated as OH-PA within 46 h after ingestion. Therefore, OH-PA represents a major metabolite of the oxidative metabolism pathway. Elimination kinetics of OH-PA is similar to the oxidative metabolites N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-cysteine (GAMA) and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-cysteine (iso-GAMA). The major excretion of d(3)-OH-PA took place between 8 and 22 h with the highest urinary d(3)-OH-PA concentration (c (max)) of 69.3 µg/L urine, 18 h (t (max)) postdose. OH-PA (5.4%), together with the other known urinary metabolites of the oxidative pathway GAMA (4.6%) and iso-GAMA (0.8%), represents 10.8% of the total AA dose. The share of the oxidative pathway metabolites is much smaller than the share of the reductive pathway metabolite N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) that represents 51.7% of the ingested d(3)-AA dose. However, this new quantitative human data on OH-PA together with the previous data on the other oxidative pathway metabolites are of special importance when evaluating the carcinogenic potential of AA and when comparing human data with data from animal studies.

Extracapsular lymph node spread: a new prognostic factor in gastric cancer.

BACKGROUND: Lymphatic spread is 1 of the most relevant prognostic factors for gastric carcinoma. The current International Union Against Cancer (UICC) pN staging system is based on the number of metastatic lymph nodes and does not take into consideration the characteristics of the metastatic lymph nodes itself. The aim of the current study was to examine the prognostic value of extracapsular lymph node involvement in gastric cancer and to find correlations with clinicopathological parameters. METHODS: Tissue samples were obtained from 159 gastric cancer patients who underwent gastrectomy with D2-lymphadenectomy in 142 (89.3%) cases and subtotal gastrectomy with D2-lymphadenectomy in 17 (10.7%) cases. The number of resected lymph nodes, number of metastatic lymph nodes, and number of metastatic lymph nodes with extracapsular lymph node involvement were determined. Extracapsular spread was defined as infiltration of cancer cells beyond the capsule of the metastatic lymph node. RESULTS: Ninety-six (60.4%) patients had lymph node metastasis. In 57 (35.8%) cases, extracapsular lymph node involvement was also detected. Extracapsular lymph node involvement was significantly associated with higher pN-category (P < .001), higher pM category (P = .048), and higher UICC stages (P = .001). According to the Kaplan-Meier log-rank statistical method, extracapsular lymph node involvement was significantly associated with poor survival (P = .001). In the multivariate analysis besides pT (P < .001) and R-category (P = .009), extracapsular lymph node involvement also remained as an independent prognostic factor (P = .003), whereas the UICC pN-category (P = .822) lost its prognostic value. CONCLUSIONS: Extracapsular lymph node involvement is associated with higher tumor stages and is an independent negative prognostic factor in gastric cancer. In future staging systems for gastric cancer, extracapsular lymph node involvement should be considered.

N-Acetyl-S-(1-carbamoyl-2-hydroxy-ethyl)-L-cysteine (iso-GAMA) a further product of human metabolism of acrylamide: comparison with the simultaneously excreted other mercaptuic acids.

The N-acetyl-S-(1-carbamoyl-2-hydroxy-ethyl)-L: -cysteine (iso-GAMA) could be identified as a further human metabolite of acrylamide. In this study, we report the excretion of d(3)-iso-GAMA in human urine after single oral administration of deuterium labelled acrylamide (d(3)-AA). One healthy male volunteer ingested a dose of about 1 mg d(3)-AA which is equivalent to a dose of 13 microg/kg bodyweight. Over a period of 46 h the urine was collected and the d(3)-iso-GAMA levels analysed by LC-ESI-MS/MS. The excretion of iso-GAMA begins five hours after application. It rises to a maximum concentration (c (max)) of 43 microg/l which was quantified in the urine excreted after 22 h (t (max)). The excretion pattern is parallel to that of the major oxidative metabolite N-acetyl-S-(2-carbamoyl-2-hydroxy-ethyl)-L-cysteine (GAMA). Total recovery of iso-GAMA was about 1% of the applied dose. Together with N-acetyl-S-(2-carbamoylethyl)-L: -cysteine (AAMA) and GAMA, 57% of the applied dose is eliminated as mercapturic acids. The elimination kinetics of the three mercapturic acids of AA are compared. We show that dietary doses of acrylamide (AA) cause an overload of detoxification via AAMA and lead to the formation of carcinogenic glycidamide (GA) in the human body.

Acrylamide in children--exposure assessment via urinary acrylamide metabolites as biomarkers.

UNLABELLED: Acrylamide (AA), a substance classified as probably carcinogenic to humans, was detected for the first time in food products in 2002. AA can be primarily found in foods containing carbohydrates and proteins, where it is formed during the heating process. Exposure assessment based on food consumption data revealed an average daily intake of AA between 0.3 and 0.8 microg/kg BW/day. These data have been confirmed by human biomonitoring using haemoglobin adducts of AA in blood or the specific mercapturic acids in urine. However, human biomonitoring data on the internal exposure of children were only sporadically available. Especially data about the excretion of both relevant mercapturic acids were missing. The mercapturic acids other than the haemoglobin adducts give the recent AA exposure of the last 24h. In this study, we quantify the internal exposure of AA and the genotoxic metabolite glycidamide (GA) in 110 children with regard to their exposure through diet and/or environmental tobacco smoke. MATERIAL AND METHODS: Hundred and ten 5-6-year-old children were randomly selected. Their dietary habits as well as their exposure to the environmental tobacco smoke were assessed by means of a questionnaire. By means of spot urine samples, mercapturic acids of acrylamide (AAMA) and mercapturic acids of glycidamide (GAMA) were analysed with LC-ESI-MS/MS. RESULTS: Median (95th percentile) urinary levels were 36.0 (152.7) microg AAMA/l and 13.4 (55.9) microg GAMA/l. Based on the metabolite levels, the median uptake of acrylamide was calculated to be 0.54 microg/kg BW/d. A number of associations with the consumption of French fries, various potato products, as well as fried cereals could be found. Significant results were found for French fries. No correlations between the exposure to environmental smoke and cotinine levels in urine were found. CONCLUSION: This is the first study to show the presence of AAMA and GAMA in urine specimens of 110 children, thus providing evidence for a background exposure by nutrition. Median (95th percentile) uptake of AA in children was 0.54 (1.91) microg/kg bodyweight and day, exceeding exposure in adults by 50%. These findings support the efforts to minimize AA formation and contamination in food. Comparing our findings with that of other human studies, there are hints that children have a higher AA intake than adults and that children more effectively oxidize AA. Both findings indicate that children might be the most vulnerable group of the population.

A spectroscopic characterization and quantification of m(III)/clay mineral outer-sphere complexes.

For the long-term safety assessment of deep radioactive waste repositories an understanding of the interactions of actinides with mineral surfaces at a molecular level is necessary. The retention/mobility of the released radionuclides is strongly dependent on sorption/desorption reactions at mineral surfaces. Thus, a quantitative understanding of the uptake mechanisms of actinides on clay minerals will make an important contribution to long-term safety assessments. Using time-resolved laser fluorescence spectroscopy (TRLFS), it was possible to differentiate between nonsorbed aquo ions and outer-sphere sorbed Cm(III) onto different montmorillonites. In addition, Cm(III)/clay outer-sphere complexation at different ionic strengths using NaCI as the background electrolyte is quantified. Finally, the results are verified by sorption model calculations.

Hemoglobin adducts and mercapturic acid excretion of acrylamide and glycidamide in one study population.

The aim of this study was to determine the relationship between the oxidative and reductive metabolic pathways of acrylamide (AA) in the nonsmoking general population. For the first time both the blood protein adducts and the urinary metabolites of AA and glycidamide (GA) were quantified in an especially designed study group with even distribution of age and gender. The hemoglobin adducts N-carbamoylethylvaline (AAVal) and N-( R, S)-2-hydroxy-2-carbamoylethylvaline (GAVal) were detected by GC-MS/MS in all blood samples with median levels of 30 and 34 pmol/g of globin, respectively. Concentrations ranged from 15 to 71 pmol/g of globin for AAVal and from 14 to 66 pmol/g of globin for GAVal. The ratio GAVal/AAVal was 0.4-2.7 (median = 1.1). The urinary metabolites were determined by LC-MS/MS. Of all urine samples examined 99% of N-acetyl- S-(2-carbamoylethyl)- l-cysteine (AAMA) levels and 73% of N-( R/ S)-acetyl- S-(2-carbamoyl-2-hydroxyethyl)- l-cysteine (GAMA) levels were above the LOD (1.5 microg/L). Concentrations ranged from

Comparison of reversed-phase liquid chromatography and hydrophilic interaction/cation-exchange chromatography for the separation of amphipathic alpha-helical peptides with L- and D-amino acid substitutions in the hydrophilic face.

Mixed-mode hydrophilic interaction/cation-exchange chromatography (HILIC/CEX) is a novel high-performance technique which has excellent potential for peptide separations. Separations by HILIX/CEX are carried out by subjecting peptides to linear increasing salt gradients in the presence of high levels of acetonitrile, which promotes hydrophilic interactions overlaid on ionic interactions with the cation-exchange matrix. In the present study, HILIC/CEX has been compared to reversed-phase liquid chromatography (RP-HPLC) for separation of mixtures of diastereomeric amphipathic alpha-helical peptide analogues, where L- and D-amino acid substitutions were made in the centre of the hydrophilic face of the amphipathic alpha-helix. Unlike RP-HPLC, temperature had a substantial effect on HILIC/CEX of the peptides, with a rise in temperature from 25 to 65 degrees C increasing the retention times of the peptides as well as improving resolution. Our results again highlight the potential of HILIC/CEX as a peptide separation mode in its own right as well as an excellent complement to RP-HPLC.