Cancer risks and hormonal modifiers of risks in BRCA1 and BRCA2 mutation carriers: Knowing the genes, what are the risks?

Leeuwen, F.E. [Promotor]van Veer, L.J. van 't [Promotor]Rookus, M.A. [Copromotor

Invited Paper: Instruction Set Extensions for Post-Quantum Cryptography

Quantum computing is one of the latest breakthroughs in the field of computer science, having the potential of breaking the underlying assumptions of public-key cryptography. With the National Institute of Standards and Technology (NIST) having announced that lattice-based Kyber as Key Encapsulation Mechanism (KEM) and Dilithium and Falcon as digital signatures are going to be standardized as the first Post-Quantum Cryptography (PQC) schemes, the scientific community needs to investigate how to efficiently implement these new primitives to ensure a smooth transition. We review in this work the state-of-the-art in Instruction Set Extensions (ISEs) for the lattice-based PQC schemes to be standardized. We categorize them into three groups. Firstly, tightly-integrated implementations that aim to be small and only accelerate the core functions, secondly more generic and bigger ISEs that target more lattice operations, and thirdly a special class that focuses on vectorized processing. While we observe promising results in improving on runtime and energy consumption, the memory footprint is often overlooked in the evaluation, even though this is a serious issue in PQC where keys, ciphertexts and signatures tend to be larger. Additionally, we envision that more generic lattice-based ISEs will surface, and that side-channel and fault attacks will become more important

Quantification of human complement C2 protein using an automated turbidimetric immunoassay

Background: The measurement of complement components is clinically useful where a deficiency is suspected, or where excessive activation and consumption are present in disease. C2 deficiency carries an increased risk of developing systemic lupus erythematosus, recurrent infections and atherosclerosis. In this study, we have evaluated The Binding Site’s Human Complement C2 SPAPLUS® assay. Methods: Linearity was tested using 13 sample dilutions covering the standard measuring range. Within- and between-assay variabilities were calculated using five samples with different C2 concentrations. The correlation between C2 concentrations in EDTA-plasma and serum was assessed, as was the correlation between C2 measurements by the automated assay and radial immunodiffusion. C2 concentrations were compared with CH50 activity, and quantified in individuals with homozygous or heterozygous C2 deficiency, acquired angioedema and patients with chronic inflammatory conditions. Results: The assay was linear across the measuring range (3.8–42.3 mg/L). Intra- and interassay variability were 2.3%–3.8% and 0%–3.3%, respectively. Comparison between C2 measurements in EDTA-plasma and serum provided a strong correlation (p<0.0001, R2=0.82, slope 0.92), as did the correlation between the automated and radial immunodiffusion methods (p<0.0001, R2=0.89, slope 1.07). A positive correlation between C2 concentration and CH50 activity was demonstrated (p<0.0001, R2=0.48). Significant differences were observed between the median C2 concentrations obtained in healthy controls and the patient clinical samples, with homozygous C2-deficient patients giving below detectable results. Conclusions: This C2 SPAPLUS® assay allows the automated, rapid and precice quantification of complement C2 protein and could therefore be considered as a replacement for older, more time-consuming methods

Association between allergen component sensitisation and clinical allergic disease in children

Background: Allergen component sensitisation testing is becoming increasingly important in the diagnosis of peanut allergy. The aim of the present study was to evaluate the relationship between sensitisation and symptoms of allergic disease in children by testing a large panel of inhalants, food allergens, and allergen components. Methods: For 287 children visiting our laboratory for allergy testing, symptoms of allergic disease were recorded by standardised validated questionnaires. Specific IgE to 11 whole allergens was assessed by ImmunoCAP, and to 112 allergen components by ISAC ImmunoCAP assay. We used latent class analysis (LCA) to distinguish clinical phenotypes. Results: Inhalant and food allergen sensitisation was common, irrespective of the children's allergic symptom type. Less than 10% of the variance in symptom scores was explained by variations in the number of allergens (components) that the child was sensitised to. In LCA, 135 children (50.2%) had mild allergy, with few symptoms and sensitisation to no or few allergens, 74 children (27.5%) had more symptoms and sensitisation to inhalant allergens (respiratory allergy) and 60 children (22.3%) showed polysensitisation to a median of six allergens and had more severe symptoms of different organ systems. Adding allergen component test results to LCA failed to result in identifiable classes of allergic disease in children. Conclusions: In this group of children with allergic symptoms, referred for allergy testing by their physician, broad screening for allergen component sensitisation did not contribute to distinguishing phenotypes of allergic disease. (C) 2022 Codon Publications. Published by Codon Publications

Data Under Siege: The Quest for the Optimal Convolutional Autoencoder in Side-Channel Attacks

Encryption is a method to keep our data safe from third parties. However, side-channel information may be leaked during encryption due to physical properties. This information can be used in side-channel attacks to recover critical values such as the secret encryption key. To this end, it is necessary to understand the robustness of implementations to assess the security of data handled by a device. Side-channel attacks are one such method which allow researchers to evaluate the robustness of implementations using appropriate metrics.In the security community, machine learning is playing a prominent role in the study of side-channel attacks. A notable example of this is the use of Convolutional Autoencoders (CAE) as a preprocessing step on the measurements. In this work we study in depth the problem of finding the most suitable architecture of such Convolutional Autoencoders. To this end, Optuna is used to explore the CAE hyperparameter space. This process allows us to identify hyperparameters that outperform state-of-the-art autoencoders, reducing the needed traces for a succesful attack by approximately 37% in the presence of Gaussian noise and reducing the trainable parameters needed to attack desynchronization by a factor of 29. In addition to the promising results, experiments carried out in this paper allow a better understanding of the hyperparameter space in the field of side channel attacks, providing a solid base for future use of CAE in this specific domain

Post-operative Day 1 Serum Transaminase Levels in Relation to Morbidity After Liver Resection

Background Post-operative serum transaminases have been proposed as possible early predictors of morbidity after liver resection. This study aimed to verify the clinical value of post-operative serum transaminases. Methods Clinical data from 2001 to 2016 in a single non-academic referral HPB center were collected from a prospectively held database. Post-operative day 1 serum aspartate transaminase (AST) and alanine transaminase (ALT) were tested for their relationship with post-operative major morbidity, defined by a Clavien-Dindo score 3 or higher, and mortality. Results For this analysis, 371 patients were included, including 149 (40%) undergoing major liver resections. In total, 17% of the patients developed major morbidity. Stepwise logistic regression demonstrated that AST, and not ALT, is an independent predictor for major morbidity (p = 0.017). The probability of major morbidity significantly increased with increasing AST values. A threshold value of 242 U/L was found to be predictive for one or more major complications. Conclusions In this study, post-operative serum AST on day 1 was a predictive factor for major morbidity after liver resection. For patients with low AST value, early discharge could be considered. However, because of the substantial inter-individual variability of AST values, more studies are needed to translate these results into clinical practice

Timing of restoration of bowel continuity after decompressing stoma, in left-sided obstructive colon cancer:a nationwide retrospective cohort

BACKGROUND: With the increasing use of decompressing stoma as a bridge to surgery for left-sided obstructive colon cancer (LSOCC), the timing of restoration of bowel continuity (ROBC) is a subject of debate. There is a lack of data on immediate ROBC during elective resection as an alternative for a 3-stage procedure. This study analysed if immediate ROBC during tumour resection is safe and of any benefit for patients who underwent decompressing stoma for LSOCC. METHODS: In a Dutch nationwide collaborative research project, 3153 patients who underwent resection for LSOCC in 75 hospitals (2009-2016) were identified. Extensive data on disease and procedural characteristics, and outcomes was collected by local collaborators. For this analysis, 332 patients who underwent decompressing stoma followed by curative resection were selected. Immediate ROBC during tumour resection was compared to two no immediate ROBC groups, (1) tumour resection with primary anastomosis (PA) with leaving the decompressing stoma in situ, and (2) tumour resection without PA. RESULTS: Immediate ROBC was performed in 113 patients (34.0%) and no immediate ROBC in 219 patients [168 with PA (50.6%) and 51 patients without PA (15.4%)]. No differences at baseline between the groups were found for age, ASA score, cT, and cM. Major surgical complications (8.8% immediate ROBC vs. 4.8% PA with decompressing stoma and 7.8% no PA; P =0.37) and mortality (2.7% vs. 2.4% and 0%, respectively; P =0.52) were similar. Immediate ROBC resulted in a shorter time with a stoma (mean 41 vs. 240 and 314 days, respectively; P &lt;0.001), and fewer permanent stomas (7% vs. 21% and 80%, respectively; P &lt;0.001) as compared to PA with a decompressing stoma or no PA. CONCLUSION: After a decompressing stoma for LSOCC, immediate ROBC during elective resection appears safe, reduces the total time with a stoma and the risk of a permanent stoma.</p

Downward trends in the prevalence of childhood overweight in two pilot towns taking part in the VIASANO community-based programme in Belgium: data from a national school health monitoring system

Background Multilevel approaches involving environmental strategies are considered to be good practice to help reduce the prevalence of childhood overweight. Objectives The objective of this study was to evaluate the effects of VIASANO, a community-based programme using the EPODE methodology, on the prevalence of overweight in two pilot towns in Belgium. Methods We analysed data from a national school health monitoring system to compare changes in the prevalence of overweight and obesity over a 3-year period (2007–2010) in children aged 3–4 and 5–6 years in the pilot towns with those of children of the same ages from the whole French-speaking community of Belgium. Heights and weights of all participants were measured by trained school nurses using a standardized method. Results The prevalence of overweight (−2.1%) and overweight + obesity (−2.4%) decreased in the pilot towns, but remained stable in the comparison population (+0.1% and +0.2%, respectively). After adjustment for lack of homogeneity between the study populations, there was a trend towards a decrease in overweight (P = 0.054) and overweight + obesity (P = 0.058) in the pilot towns compared with the general population. Conclusions These results suggest that a community-based programme, such as VIASANO, may be a promising strategy for reducing the prevalence of childhood overweight even over a short period of time

Alteration of the Exhaled Volatile Organic Compound Pattern in Colorectal Cancer Patients after Intentional Curative Surgery—A Prospective Pilot Study

As current follow-up modalities for colorectal carcinoma (CRC) have restricted sensitivity, novel diagnostic tools are needed. The presence of CRC changes the endogenous metabolism, resulting in the release of a specific volatile organic compounds (VOC) pattern that can be detected with an electronic nose or AeonoseTM. To evaluate the use of an electronic nose in the follow-up of CRC, we studied the effect of curative surgery on the VOC pattern recognition using AeonoseTM. A prospective cohort study was performed, in which 47 patients diagnosed with CRC were included, all of whom underwent curative surgical resection. Breath testing was performed before and after surgery using the AeonoseTM. A machine learning model was developed by discerning between the 94 pre-and postoperative breath samples. The training model differentiated between the pre-and postoperative CRC breath samples with a sensitivity and specificity of 0.78 (95%CI 0.61–0.90) and 0.73 (95%CI 0.56–0.86), respectively, with an accuracy of 0.76 (95%CI 0.66–0.85), and an area under the curve of 0.79 (95%CI 0.68–0.89). The internal validation of the test set resulted in an accuracy of 0.75 (95%CI 0.51–0.91) and AUC of 0.82 (95%CI 0.61–1). In conclusion, our results suggest that the VOC pattern of CRC patients is altered by curative surgery in a short period, indicating that the exhaled VOCs might be closely related to the presence of CRC. However, to use AeonoseTM as a potential diagnostic tool in the clinical follow-up of CRC patients, the performance of the models needs to be improved through further large-scale prospective research.</p