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Background: Pancreatic ductal adenocarcinoma (PDAC) is notorious for its poor prognosis even after curative resection. Responses to immunotherapy are rare and related to inadequate T-cell priming. We previously demonstrated the potency of allogeneic lysatedendritic cell (DC) vaccination in a preclinical model. Here we translate this concept to patients.Methods: In this phase I study, patients with resected PDAC were included when they demonstrated no radiologic signs of recurrence after standard-of-care treatment. Allogeneic tumour lysate-loaded autologous monocyte-derived DCs were injected at weeks 0, 2, 4 and at months 3 and 6. Objectives are feasibility, safety and immunogenicity of allogeneic tumour-DCs. The presence of tumour antigens shared between the vaccine and patient tumours was investigated. Immunological analyses were performed on peripheral blood, skin and tumour.Results: Ten patients were included. DC production and administration were successful. All patients experienced a grade 1 injection-site and infusion-related reaction. Two patients experienced a grade 2 fever and 1 patient experienced a grade 3 dyspnoea. No vaccine-related serious adverse events were observed. Shared tumour antigens were found between the vaccine and patient tumours. All evaluated patients displayed a vaccine-induced response indicated by increased frequencies of Ki67+ and activated PD-1+ circulating T-cells. In addition, treatment-induced T-c ell reactivity to autologous tumour of study patients was detected. Seven out of ten patients have not experienced disease recurrence or progression at a median follow-up of 25 months (15-32 months).Conclusion: Allogeneic tumour lysate-DC treatment is feasible, safe and induces immune reactivity to PDAC expressed antigens. 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

RATIONALE The analysis of the nitrogen (N) isotopic composition of organic matter bound to30fossil biomineral structures (BB-δ 15 N) using the oxidation-denitrifier (O-D) method provides anovel tool to study past changes in N cycling processes.METHODS We report a set of methodological improvements to the O-D method, including: (i) amethod for sealing the reaction vials in which oxidation of organic N to NO3- takes place; (ii) arecipe for bypassing the pH adjustment step before the bacterial conversion of NO3- to N2 O; and35(iii) a storage method of recrystallized dipotassium peroxodisulphate (K2 S 2 O8 ) under Aratmosphere.RESULTS The new method eliminates the occasional contamination and vial breakage, andincreases sample throughput. The protocol for bypassing of pH adjustment does not affect BB-δ 15 N, and it significantly reduces processing time. Storage of K2 S2 O8 reagent under Ar atmosphere40produces stable oxidation blanks over more than two years. We report analytical blanks, accuracyand precision for this methodology from eight users over the course of ~ 3.5 years of analyses atthe Max Planck Institute for Chemistry. Our method produces analytical blanks characterized bylow N content (0.30 ± 0.13 nmol N, 1σ, n=204) and stable δ 15 N (– 2.45 ± 3.50 ‰, n=204). Theanalysis of reference amino acid standards USGS40 and USGS65 indicates an overall accuracy of45– 0.23 ± 0.35 ‰ (1σ, n=891). The analysis of in-house fossil standards gives similar analyticalprecision (1σ) across a range of BB-δ 15 N values and biominerals: zooxanthellate coral standardPO-1 (6.08 ± 0.21 ‰, n=267), azooxanthellate coral standard LO-1 (10.20 ± 0.28 ‰, n=258),foraminifera standard MF-1 (5.92 ± 0.28 ‰, n=243) and tooth enamel AG-Lox (4.06 ± 0.49 ‰,n=78).50CONCLUSIONS The proposed analytical improvements significantly increase samplethroughput without compromising analytical precision or accuracy down to 1 nmol of N. Submitted to Rapid Communications in Mass Spectrometry

Contains fulltext : 245471.pdf (Publisher’s version ) (Open Access) 107 p.

BACKGROUND: Efavirenz is well known for its clinical cognitive side-effects. Even asymptomatic patients who switch for other reasons than neurocognitive complaints have reported a subjective improvement in cognitive functioning after discontinuing Efavirenz. The aim of this study was to assess the effect on cognition of switching Atripla (TDF/FTC/EFV) to Eviplera (TDF/FTC/RPV), hypothesizing an improvement when discontinuing Efavirenz. SETTING: a randomized controlled design with a highly comparable comparator drug was used to minimize bias and to differentiate drug- versus learning effects. An extensive sensitive neuropsychological assessment (NPA) was used to detect subtle changes. METHODS: virologically suppressed, cognitively asymptomatic male HIV-infected patients on Atripla were included and randomized (2:1) to switch to Eviplera (switch group) or continue on Atripla (control group) for 12 weeks. At baseline and week 12, patients underwent an extensive NPA. RESULTS: 14 control and 34 switch subjects completed the study. There were no differences at baseline. Group-analysis demonstrated a significantly better improvement for the switch group on the domains attention (p=0.041) and speed of information processing (p=0.014). Normative comparison analyses showed that 5 out of the 34 patients who switched (15%) improved on NPA-score as compared to the control group. Interestingly, subjective improvement after discontinuing Efavirenz made 74% of the switch group chose for a regime without Efavirenz after study completion. CONCLUSION: switching from Atripla to Eviplera resulted in objective cognitive improvement on group level in cognitively asymptomatic patients. Discrepancies in objective and subjective cognitive complaints make it challenging to identify patients that would benefit from discontinuing Efavirenz.

To enhance the transparency, accountability and efficiency of the Dutch Ministry of Justice and Security, the ministry has set up an open data program to proactively stimulate sharing its (public-funded) data sets with the public or with other organi-sations. Disclosure of personal data is considered as one of the main threats for data opening. This study, as one activity within the open data program, aims at investigating Statistical Disclosure Control (SDC) tools and methods for protecting personal data. More specifically, the main objective of the study is to provide in-sights in the main functionalities provided by SDC technologies so that data control-lers can be supported in their decision-making processes related to storing, sharing, and opening the ministry’s personal data. To this end, the study context is tuned to the ministry’s settings and requirements. This deliverable presents the acquired insights, particularly for three selected open source SDC tools (namely: μ-ARGUS, ARX and sdcMicro).

Using a task approach, this study examined the extent to which employee regulatory focus would “gravitate” employees towards promotion- versus prevention-oriented tasks within their jobs, and whether a subsequent regulatory fit/misfit would be associated with their well-being (i.e., mental health and job satisfaction). In a pre-study among 37 employees, we determined the regulatory focus of work tasks from the Netherlands Skill Survey, which are relevant to the general working population, resulting in a selection of 7 promotion and 11 prevention tasks. For our main study, we used the Dutch Longitudinal Internet Studies for the Social Sciences (LISS) panel and collected data from 1,606 respondents. In 2011, we collected respondents’ regulatory focus and in 2012, we collected their work tasks and well-being. Promotion-oriented employees considered both promotion and prevention tasks to be highly relevant in their jobs, and this relevance was associated with their mental health. Prevention-oriented employees, however, did not respond to the relevance of promotion or prevention tasks and generally reported lower well-being, irrespective of the regulatory focus of their tasks. We tentatively conclude that promotion focus gravitates employees towards job with a richer task content, containing both promotion and prevention tasks. © 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Attentional bias variability may be related to alcohol abuse. Of potential use for studying variability is the anticipatory attentional bias: Bias due to the locations of predictively-cued rather than already-presented stimuli. The hypothesis was tested that conflicting automatic associations are related to attentional bias variability. Further, relationships were explored between anticipatory biases and individual differences related to alcohol use. 74 social drinkers performed a cued Visual Probe Task and univalent Single-Target Implicit Associations Tasks. Questionnaires were completed on risky drinking, craving, and motivations to drink or refrain from drinking. Conflict was related to attentional bias variability at the 800 ms Cue-Stimulus Interval. Further, a bias related to craving and risky drinking was found at the 400 ms Cue-Stimulus Interval. Thus, the selection of attentional responses was biased by predicted locations of expected salient stimuli. The results support a role of conflicting associations in attentional bias variability.

The monetary incentive delay task breaks down reward processing into discrete stages for fMRI analysis. Here we look at anticipation of monetary gain and loss contrasted with neutral anticipation. We meta-analysed data from 15 original whole-brain group maps (n = 346) and report extensive areas of relative activation and deactivation throughout the whole brain. For both anticipation of gain and loss we report robust activation of the striatum, activation of key nodes of the putative salience network, including anterior cingulate and anterior insula, and more complex patterns of activation and deactivation in the central executive and default networks. On between-group comparison, we found significantly greater relative deactivation in the left inferior frontal gyrus associated with incentive valence. This meta-analysis provides a robust whole-brain map of a reward anticipation network in the healthy human brain. Electronic supplementary material The online version of this article (10.1007/s11065-018-9385-5) contains supplementary material, which is available to authorized users.