Food Processing does not Abolish the Allergenicity of the Carrot Allergen Dau c 1 : Influence of pH, Temperature and the Food Matrix

SCOPE: The major carrot allergen Dau c 1 belongs to the group of pathogenesis related class 10 (PR-10) proteins and is homologous to the birch pollen allergen Bet v 1. In contrast to most other PR-10 allergens, Dau c 1 can elicit Bet v 1 independent sensitization. Although Dau c 1 is considered heat labile, allergic reactions against cooked carrots are possible. METHODS AND RESULTS: The pH and temperature stability as well as the allergenic potential before and after treatment of purified natural (n) Dau c 1 and different recombinant (r) isoallergens is investigated: rDau c 1.0104, rDau c 1.0105, rDau c 1.0201, rDau c 1.0301. All proteins except rDau c 1.0201 are able to refold at physiological pH. pH conditions around the pI (4.4–5.5) or the presence of the carrot matrix reduce the refolding capacity. Below the pI, most isoallergens are heat resistant and still able to cause mediator release, indicating allergenicity. Moreover, cooked carrot extract is still able to provoke mediator release due to remaining soluble Dau c 1. CONCLUSION: Patients allergic to carrots should avoid processed carrot containing foodstuff because heating or pH treatment do not completely abolish the allergenicity of Dau c 1

E‐ARK Search, Access and Display Interfaces

The aim of this report is to describe the “Search, Access and Display Interfaces” that have been developed in the Access component of the E-ARK project. The deliverable associated with this report is mainly a software deliverable and therefore this document provides only underpinning descriptions of and links to the software itself. The tools that are described and provided allow Consumers (ie. end-users and archivists) to: 1. Search and order records (primarily end-users, but also archivists) 2. Manage orders of records and manage the records themselves, including the AIP to DIP conversion (archivists only) 3. Access ordered records as DIPs (primarily end-users, but also archivists) In addition to the the introductory remarks in chapter 2, the functionality of the tools that allow the Consumers to search, manage, and access records is described in chapter 3. After the description of each tool, links are provided to code and documentation

Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

BackgroundHistologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.MethodsThis was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0–4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0–2 vs F3 vs F4; LSM: 2·67; NFS: 0·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.FindingsOf 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44–63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33–91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001 for all comparisons). The tAUC at 5 years were 0·72 (95% CI 0·62–0·81) for histology, 0·76 (0·70–0·83) for LSM-VCTE, 0·74 (0·64–0·82) for FIB-4, and 0·70 (0·63–0·80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression.InterpretationSimple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases

Cause and effect : Relationships in Sweden's county councils and regions' balanced scorecards

Syfte: Syftet med uppsatsen är att analysera hur Sveriges landsting och regioner formulerar och visualiserar orsak-verkan-samband mellan perspektiven vid tillämpning av balanserat styrkort. Metod: Uppsatsen använder sig av en kvantitativ innehållsanalys med en dokumentstudie av Sveriges landsting och regioners årsredovisningar och budgetdokument för år 2015. Slutsatser: Av Sveriges landsting och regioner tillämpar 11 av 21 balanserat styrkort som styrmodell. Landstingen och regionernas balanserade styrkort uppnår i relativt hög grad orsak-verkan-samband, dock presenteras orsak-verkan-samband i mycket låg utsträckning för verksamhetens intressenter. Sveriges Landsting och regioner presenterar ingen form av strategikarta som uppfyller rekvisiten som ställs på en strategikarta. Vidare visar författarna att tidsperspektivet mellan perspektiven påverkas av förhållandet mellan utfallsmått och drivande mått i varje perspektiv. En hög andel utfallsmått placerar perspektivet högt upp i det balanserade styrkortet och en hög andel drivande mått placerar perspektivet långt ner i det balanserade styrkortet.Purpose: The purpose of the thesis is to analyse how Sweden's county councils and regions phrases and visualizes the cause and effect relationship between the perspectives in the implementation of the balanced scorecard. Method: This thesis uses a quantitative content analysis with a document study of Sweden's county councils and regions financial statement and budget documents for the year 2015. Conclusions: 11 of 21 of Sweden's county councils and regions are using balanced scorecard as governance model. The county councils and regions’ balanced scorecards are demonstrating a relatively high degree of cause and effect relationship. However, this is not presented to the organization's stakeholders. Sweden's county councils and regions does not present any form of strategy map that fulfills the demands that is required of a strategy map. The authors also finds that the time dimension between the perspectives is affected by the mixture of outcome measures and performance drivers in each of the perspectives. A high proportion of outcome measures will place the perspective high up in the balances scorecard. A high proportion performance drivers will place the perspective lower in the balanced scorecard

Food Processing Does Not Abolish the Allergenicity of the Carrot Allergen Dau c 1: Influence of pH, Temperature, and the Food Matrix

SCOPE: The major carrot allergen Dau c 1 belongs to the group of pathogenesis related class 10 (PR-10) proteins and is homologous to the birch pollen allergen Bet v 1. In contrast to most other PR-10 allergens, Dau c 1 can elicit Bet v 1 independent sensitization. Although Dau c 1 is considered heat labile, allergic reactions against cooked carrots are possible. METHODS AND RESULTS: The pH and temperature stability as well as the allergenic potential before and after treatment of purified natural (n) Dau c 1 and different recombinant (r) isoallergens is investigated: rDau c 1.0104, rDau c 1.0105, rDau c 1.0201, rDau c 1.0301. All proteins except rDau c 1.0201 are able to refold at physiological pH. pH conditions around the pI (4.4–5.5) or the presence of the carrot matrix reduce the refolding capacity. Below the pI, most isoallergens are heat resistant and still able to cause mediator release, indicating allergenicity. Moreover, cooked carrot extract is still able to provoke mediator release due to remaining soluble Dau c 1. CONCLUSION: Patients allergic to carrots should avoid processed carrot containing foodstuff because heating or pH treatment do not completely abolish the allergenicity of Dau c 1

Prevalence and correlation of cytokine-specific autoantibodies with epidemiological factors and C-reactive protein in 8,972 healthy individuals: Results from the Danish Blood Donor Study

<div><p>Natural cytokine-specific autoantibodies (c-aAb) have been measured in healthy and diseased individuals, and have been considered as both endogenous immune-regulators and pathogenic factors. Overall, the etiology and potential pathology of c-aAb are still undefined. To further characterize the sero-prevalence, predictors and consequences of high c-aAb levels, we performed the largest population-based study of c-aAb to date, using participants and epidemiological data from the Danish Blood Donor Study. Using a validated bead-based multiplex assay we assessed plasma levels of IL-1α, IL-6, IL-10, IFNα and GM-CSF-specific c-aAb in 8,972 healthy blood donors. Trace levels of at least one of the investigated c-aAb could be measured in 86% of the participants. The presence of high levels of potentially inhibitory c-aAb was generally associated with increasing age and male or female sex, depending on the c-aAb in question. A negative correlation between high levels of IL-6-specific c-aAb and plasma levels of C-reactive protein was observed, indicating cytokine-neutralizing levels of c-aAb in healthy blood donors. There was no substantial correlation between high levels of the five individual c-aAb investigated in this study. These data suggest that autoimmunity against endogenous cytokines is a relatively common phenomenon in healthy individuals, and that predictive factors for high, potentially neutralizing c-aAb levels vary depending on the cytokine in question, and may differ from predictors of general c-aAb presence.</p></div

C-aAb as a predictor of CRP.

<p>A: Log-transformed CRP was used as the dependent variable in a series of linear regression analyses, with sex, age, obesity, active smoking and high levels of c-aAb as independent variables. High levels of c-aAb were defined as MFI values above the 99^th percentile. Data are presented as regression coefficients with 95% confidence intervals. B: Participant status of being CRP-low (CRP < 0.1 mg/L) was used as the binary dependent variable in a series of logistic regression analyses, with sex, age, obesity, active smoking and high levels of c-aAb as independent variables. Data are presented as OR in favor of being CRP-low, with 95% confidence intervals. ***denotes a <i>p</i> value of ≤ 0.001.</p