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Summary: Background: Despite the widely reported success of knee arthroplasty, studies show that 1.6–3 % of patients undergo revision within the first postoperative year predominantly due to infection. Preoperative skin preparation may potentially decrease the bacterial load and consequently, the risk of periprosthetic joint infections. The effects of hair removal on prosthetic joint infection are inconsistent. Our primary aim was to investigate if hair removal with a clipper influenced skin colonisation and bacterial composition. Methods: Forty Caucasian male participants who were planned to undergo knee arthroplasty, (mean age 63.8 years), were included. Patients were randomised to hair removal in a within-person study design. As a control, the opposite leg of the patient was used. Swabs were collected prior to hair removal (baseline), immediately after hair removal (Day 0), and with follow-up after one and seven days. Results: The intervention showed significant decrease in mean log colony-forming units per. cm2 from baseline 2.97 to 2.67 (P

Kamille Herskind,1 Peter Bjødstrup Jensen,1 Christina Anne Vinter,2– 4 Lone Krebs,5,6 Lene Friis Eskildsen,5 Anne Broe,1,7 Anton Pottegård,1 Mette Bliddal1,8 1Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark; 2Department of Gynaecology and Obstetrics, Odense University Hospital, Odense, Denmark; 3Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 4Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark; 5Department of Obstetrics and Gynecology, Copenhagen University Hospital-Amager and Hvidovre, Copenhagen, Denmark; 6Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 7IQVIA, London, UK; 8Research Unit OPEN, Department of Clinical Research, University of Southern Denmark, Odense, DenmarkCorrespondence: Mette Bliddal, OPEN, Heden 16, St.tv, Odense, 5000, Denmark, Tel +45 2943 7912, Email mette.bliddal@rsyd.dkPurpose: This study aimed to systematically evaluate the validity of variables related to pregnancy, delivery, and key characteristics of the infant in the Danish National Patient Register using maternal medical records as the reference standard.Patients and Methods: We reviewed medical records of 1264 women giving birth in the Region of Southern Denmark during 2017. We calculated positive (PPV) and negative (NPV) predictive values, sensitivity, and specificity to estimate the validity of 49 selected variables.Results: The PPV was ≥ 0.90 on most pregnancy-related variables including parity, pre-gestational BMI, diabetes disorders, and previous cesarean section, while it was lower for hypertensive disorders, especially mild to moderate preeclampsia (0.49, 95% CI 0.32– 0.66). Sensitivity ranged from 0.80 to 1.00 on all pregnancy-related variables, except hypertensive disorders (sensitivity 0.38– 0.71, lowest for severe preeclampsia). On most delivery-related variables including obstetric surgical procedures (eg cesarean section and induction of labor), pharmacological pain-relief, and gestational age at delivery, PPV’s ranged from 0.98 to 1.00 and the corresponding sensitivities from 0.87 to 1.00. Regarding infant-related variables, both the APGAR score registered five minutes after delivery and birthweight yielded a PPV of 1.00.Conclusion: Obstetric coding in the Danish National Patient Register shows very high validity and completeness making it a valuable source for epidemiologic research.Plain Language Summary: Danish register data are often used for epidemiological research in reproduction. The registers are based on coded information to the registers based on information from medical records. The quality of the register data is highly dependent of the validity of the codes. Yet there is a lack in our knowledge of the validity of data related to pregnancy, childbirth, and the characteristics of the newborn baby. We therefore aimed to validate the Danish National Patient Registry data related to pregnancy and childbirth by comparing the registered code with information from the medical records.We scrutinized medical records from 1264 women giving birth in the Region of Southern Denmark during 2017. We compared the registration in the medical record with the registered code in the Danish National Patient Registry by calculating how accurate the register data are according to 49 different variables.Results showed that registered codes in the Patient Registry for pregnancy- and childbirth-related conditions and key infant characteristics were to a high degree in agreement with the data from the medical report with few exceptions.In conclusion, the study revealed that the Danish National Patient Register provides highly accurate and comprehensive data for most pregnancy, delivery, and infant-related variables. This underscores the register’s value as a reliable source for epidemiologic research in reproductive health.Keywords: registries, sensitivity and specificity, validity, epidemiology, pregnancy, delivery

Abstract Background Ionotropic glutamate receptors α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR) modulate proliferation, invasion and radioresistance in glioblastoma (GB). Pharmacological targeting is difficult as many in vitro-effective agents are not suitable for in patient applications. We aimed to develop a method to test the well tolerated AMPAR- and NMDAR-antagonist xenon gas as a radiosensitizer in GB. Methods We designed a diffusion-based system to perform the colony formation assay (CFA), the radiobiological gold standard, under xenon exposure. Stable and reproducible gas atmosphere was validated with oxygen and carbon dioxide as tracer gases. After checking for AMPAR and NMDAR expression via immunofluorescence staining we performed the CFA with the glioblastoma cell lines U87 and U251 as well as the non-glioblastoma derived cell line HeLa. Xenon was applied after irradiation and additionally tested in combination with NMDAR antagonist memantine. Results The gas exposure system proved compatible with the CFA and resulted in a stable atmosphere of 50% xenon. Indications for the presence of glutamate receptor subunits were present in glioblastoma-derived and HeLa cells. Significantly reduced clonogenic survival by xenon was shown in U87 and U251 at irradiation doses of 4–8 Gy and 2, 6 and 8 Gy, respectively (p

Background Survival of infants with congenital diaphragmatic hernia (CDH) has increased and more insight is warranted on the long-term issues of this condition.Methods We conducted a cross-sectional study on consecutively born infants with CDH treated at a non-extracorporeal membrane oxygenation centre (ECMO) from 1998 to 2015. Quality of life was evaluated using the Pediatric Quality of Life Inventory Generic Core Scale 4.0 (PedsQL(4.0)) Questionnaire and an interview was conducted to assess for CDH-related morbidity.Results 71 eligible CDH survivors were identified and 51 consented to participate: aged 5–21 years, 28 (54.9%) male, 42 (82.4%) with left-sided hernias, 10 (19.6%) needed patch repair, median length of stay in hospital was 27.96 days (IQR 18.54–61.56). Forty-nine completed the questionnaire with a median PedsQL total score for participants of 82.6 vs 83.7 of the total proxy parent score (p=0.04). Total score was significantly lower for participants aged 5–12 years compared with participants aged 13–21 years (p=0.04); however, when reported by domains, only the physical score remained significantly lower (p=0.048). Two (4.1%) participants’ and 8 (16.7%) proxy parents’ scores were below 70 and considered at risk of impaired quality of life. We identified the presence of CDH-related morbidity in our population, and confirmed an association between respiratory morbidity and lower PedsQL scores (p=0.04).Conclusion We report an overall good quality of life in our population with CDH. However, a lower physical score was noted when compared with a national Danish cohort and individuals at risk of reduced quality of life were recognised. Structured follow-up programmes to identify and ensure early management of CDH-related issues may prevent a negative impact on quality of life.

High-spin states in Cs124 were populated in the Ni64(Ni64,p3n) reaction and the Gammasphere detector array was used to measure γ-ray coincidences. Both positive- and negative-parity bands, including bands with chiral configurations, have been extended to higher spin, where a shape change has been observed. The configurations of the bands before and after the alignment are discussed within the framework of the cranked Nilsson-Strutinsky model. The calculations suggest that the nucleus undergoes a shape transition from triaxial to prolate around spin I≃22 of the positive-parity states. The alignment gain of 8â.,, observed in the positive-parity bands, is due to partial alignment of several valence nucleons. This indicates the absence of band crossing due to paired nucleons in the bands.

IntroductionWe hypothesized that increasing the pelvic integral dose (ID) and a higher dose per fraction correlate with worsening fatigue and functional outcomes in localized prostate cancer (PCa) patients treated with external beam radiotherapy (EBRT).MethodsThe study design was a retrospective analysis of two prospective observational cohorts, REQUITE (development, n=543) and DUE-01 (validation, n=228). Data were available for comorbidities, medication, androgen deprivation therapy, previous surgeries, smoking, age, and body mass index. The ID was calculated as the product of the mean body dose and body volume. The weekly ID accounted for differences in fractionation. The worsening (end of radiotherapy versus baseline) of European Organisation for Research and Treatment of Cancer EORTC) Quality of Life Questionnaire (QLQ)-C30 scores in physical/role/social functioning and fatigue symptom scales were evaluated, and two outcome measures were defined as worsening in ≥2 (WS2) or ≥3 (WS3) scales, respectively. The weekly ID and clinical risk factors were tested in multivariable logistic regression analysis.ResultsIn REQUITE, WS2 was seen in 28% and WS3 in 16% of patients. The median weekly ID was 13.1 L·Gy/week [interquartile (IQ) range 10.2-19.3]. The weekly ID, diabetes, the use of intensity-modulated radiotherapy, and the dose per fraction were significantly associated with WS2 [AUC (area under the receiver operating characteristics curve) =0.59; 95% CI 0.55-0.63] and WS3 (AUC=0.60; 95% CI 0.55-0.64). The prevalence of WS2 (15.3%) and WS3 (6.1%) was lower in DUE-01, but the median weekly ID was higher (15.8 L·Gy/week; IQ range 13.2-19.3). The model for WS2 was validated with reduced discrimination (AUC=0.52 95% CI 0.47-0.61), The AUC for WS3 was 0.58,ConclusionIncreasing the weekly ID and the dose per fraction lead to the worsening of fatigue and functional outcomes in patients with localized PCa treated with EBRT.

Due to impressive performance, deep neural networks for object detection in images have become a prevalent choice. Given the complexity of the neural network models used, users of these algorithms are typically given no hint as to how the objects were found. It remains, for example, unclear whether an object is detected based on what it looks like or based on the context in which it is located. We have developed an algorithm, Surrogate Object Detection Explainer (SODEx), that can explain any object detection algorithm using any classification explainer. We evaluate SODEx qualitatively and quantitatively by detecting objects in the COCO dataset with YOLOv4 and explaining these detections with LIME. This empirical evaluation does not only demonstrate the value of explainable object detection, it also provides valuable insights into how YOLOv4 detects objects.

Crash fault tolerance describes the capability of a distributed system to maintain its proper function despite the occurrence of crashes or failures in one or more of its components. When a distributed system possesses crash fault tolerance, it can be further fortified to achieve Byzantine fault tolerance. Byzantine fault tolerance empowers a distributed system to establish consensus among participants, even when faced with faulty or malicious behavior. Consensus plays a critical role in various tasks, including determining the accurate value of a shared variable, electing a leader, or validating the integrity of a business transaction. Compared to crash fault tolerance, Byzantine fault tolerance instills greater trust because it enables consensus even in the presence of malicious entities. This paper focuses on the performance evaluation of two blockchain solutions that exhibit Byzantine fault tolerance, in contrast to a blockchain solution that demonstrates crash fault tolerance. Specifically, the paper investigates the additional performance requirements associated with the enhanced trust resulting from Byzantine fault tolerance in e-business trading on both national and transnational scales. We analyze the resources needed to operate a business-to-business/business-to-government (B2B/B2G) compliance framework in two distinct geographic scenarios. The first examines the national scale, using Denmark as an example, which is the eleventh largest European country by GDP. The second scenario considers the scale of the European Union (EU) with its 27 member states (plus the United Kingdom).

For the purpose of nature management and species conservation, European bison (Bison bonasus) are being increasingly reintroduced into nature reserves across Europe. The aim of this study was to investigate European bison’s adaptability to new areas through the study of their parasite-EPG (eggs per gram feces) and dietary diversity during twelve months after translocation. We compared the parasite-EPG from introduced European bison in Lille Vildmose, Denmark, with the parasite-EPG from populations from Bornholm, Denmark, and Białowieża Forest, Poland. From March 2021 to February 2022, fecal samples were collected from three populations. Samples from Lille Vildmose were examined through flotation, sedimentation, the Baermann technique, and nanopore sequencing. Fecal samples from Bornholm and Białowieża were examined through flotation and sedimentation. Nanopore sequencing of DNA from 63 European bison’s fecal samples collected during March–September in Lille Vildmose identified 8 species of nematodes within the digestive tract of the European bison, with Haemonchus contortus being the most frequently observed. In Lille Vildmose, a significantly higher excretion of nematode-EPG was observed during the summer period than in the spring, autumn, and winter. In addition, monthly differences in the excretion of nematode eggs were found, with this being significantly higher in June than in the months during autumn and winter (October–February). Significant differences in the nematode-EPG were only found between the excretion of nematode eggs in Białowieża Forest when compared to that of Lille Vildmose, with significantly higher excretion in Lille Vildmose (October–November). The results indicate that the development rates for nematodes may be affected by changes in temperature, with increasing temperatures speeding up their development time. Independent of this study design, wildlife vets together with the gamekeepers managing the herd found it necessary to treat the herd with antiparasitics for practical and animal welfare reasons in relation to translocation. Furthermore, 79 plant taxa were identified in the diet of the European bison. The broadest diet was observed in March suggesting that the European bison quickly adapted to their new habitat. The results suggest a seasonal shift in their diet, with this being most apparent from March to April.

Purpose: Some patients with breast cancer treated by surgery and radiation therapy experience clinically significant toxicity, which may adversely affect cosmesis and quality of life. There is a paucity of validated clinical prediction models for radiation toxicity. We used machine learning (ML) algorithms to develop and optimise a clinical prediction model for acute breast desquamation after whole breast external beam radiation therapy in the prospective multicenter REQUITE cohort study. Methods and Materials: Using demographic and treatment-related features (m = 122) from patients (n = 2058) at 26 centers, we trained 8 ML algorithms with 10-fold cross-validation in a 50:50 random-split data set with class stratification to predict acute breast desquamation. Based on performance in the validation data set, the logistic model tree, random forest, and naïve Bayes models were taken forward to cost-sensitive learning optimisation. Results: One hundred and ninety-two patients experienced acute desquamation. Resampling and cost-sensitive learning optimisation facilitated an improvement in classification performance. Based on maximising sensitivity (true positives), the “hero” model was the cost-sensitive random forest algorithm with a false-negative: false-positive misclassification penalty of 90:1 containing m = 114 predictive features. Model sensitivity and specificity were 0.77 and 0.66, respectively, with an area under the curve of 0.77 in the validation cohort. Conclusions: ML algorithms with resampling and cost-sensitive learning generated clinically valid prediction models for acute desquamation using patient demographic and treatment features. Further external validation and inclusion of genomic markers in ML prediction models are worthwhile, to identify patients at increased risk of toxicity who may benefit from supportive intervention or even a change in treatment plan.

High-spin states in Xe124 have been populated using the Se80(Ca48,4n) reaction at a beam energy of 207 MeV and high-multiplicity, γ-ray coincidence events were measured using the Gammasphere spectrometer. Six high-spin bands with large moments of inertia, similar to those observed in neighboring nuclei, have been observed. The experimental results are compared with calculations within the framework of the cranked Nilsson-Strutinsky model. It is suggested that the configurations of the bands involve excitations of protons across the Z=50 shell gap coupled to neutrons within the N=50-82 shell or excited across the N=82 shell closure.

Our transaction history in the current centralized banking system has the ability to reveal a lot of private information for each spender, both to the banking system itself, but also to those entities that surround it (e.g., governments, industry etc). Examples of leaking information constitute the amounts spent, the goods on which the amounts were spent, the spending locations and the users we exchange money with. This knowledge is powerful in the hands of those who have it, and can be used in multiple ways, not always to our benefit. Cryptocurrencies, such as the famous Bitcoin, were proposed as a means to address the limitations of centralized banking systems and to offer its users privacy with regards to their transactional data. In this work, we perform a systematic literature review on the realm of privacy for electronic currencies. We present the development of digital money from electronic cash to cryptocurrencies and focus on the techniques that are employed to enhance user-privacy. Furthermore, we present flaws of the current cryptocurrency systems, which reduce the privacy of the cryptocurrency users. Finally, we describe three research directions to enhance privacy for cryptocurrencies: transaction propagation mechanisms, succinct ZK proof systems without a trusted setup, and specialised trustless zero-knowledge proofs.

Since Bitcoin's debut in 2008, blockchain, the technology behind the cryptocurrency, has been gaining increasing scientific and industrial interest. Due to the technology's innate distributed and immutable features, the adoption of blockchains on supply chains is one of the most promising recent applications. In this survey, we review academic researches and implementations of distributed ledgers on supply chains. We present the current state of research on the subject and summarize the benefits and the challenges of the distributed organization and management of supply chains. Focusing on industrial practices and use cases, we discuss the technical characteristics and maturity of the various industrial projects. Our goal is to assess the applicability of blockchains in the supply chain domain and to provide a foundation for practitioners and researchers to direct their future projects towards improving the technology and its applications.

Colorectal cancer (CRC) is a major contributor to cancer-associated morbidity worldwide and over one-third of CRC is located in the rectum. Neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection is commonly applied to treat locally advanced rectal cancer (LARC). In this review, we summarize current and novel concepts of neoadjuvant therapy for LARC such as total neoadjuvant therapy and describe how these developments impact treatment response. Moreover, as response to nCRT is highly divergent in rectal cancers, we discuss the role of potential predictive biomarkers. We review recent advances in biomarker discovery, from a clinical as well as a histopathological and molecular perspective. Furthermore, the role of emerging predictive biomarkers derived from the tumor environment such as immune cell composition and gut microbiome is presented. Finally, we describe how different tumor models such as patient-derived cancer organoids are used to identify novel predictive biomarkers for chemoradiotherapy (CRT) in rectal cancer.

In prostate cancer (PCa), a characteristic stromal–epithelial redistribution of the membrane protein caveolin 1 (CAV1) occurs upon tumor progression, where a gain of CAV1 in the malignant epithelial cells is accompanied by a loss of CAV1 in the tumor stroma, both facts that were correlated with higher Gleason scores, poor prognosis, and pronounced resistance to therapy particularly to radiotherapy (RT). However, it needs to be clarified whether inhibiting the CAV1 gain in the malignant prostate epithelium or limiting the loss of stromal CAV1 would be the better choice for improving PCa therapy, particularly for improving the response to RT; or whether ideally both processes need to be targeted. Concerning the first assumption, we investigated the RT response of LNCaP PCa cells following overexpression of different CAV1 mutants. While CAV1 overexpression generally caused an increased epithelial-to-mesenchymal phenotype in respective LNCaP cells, effects that were accompanied by increasing levels of the 5′-AMP-activated protein kinase (AMPK), a master regulator of cellular homeostasis, only wildtype CAV1 was able to increase the three-dimensional growth of LNCaP spheroids, particularly following RT. Both effects could be limited by an additional treatment with the SRC inhibitor dasatinib, finally resulting in radiosensitization. Using co-cultured (CAV1-expressing) fibroblasts as an approximation to the in vivo situation of early PCa it could be revealed that RT itself caused an activated, more tumor-promoting phenotype of stromal fibroblats with an increased an increased metabolic potential, that could not be limited by combined dasatinib treatment. Thus, targeting fibroblasts and/or limiting fibroblast activation, potentially by limiting the loss of stromal CAV1 seems to be absolute for inhibiting the resistance-promoting CAV1-dependent signals of the tumor stroma.

Excited states in Lu167 were populated in the Sb123(Ca48,4n) reaction at 203 MeV and decay γ rays measured using the Gammasphere spectrometer array. Two triaxial strongly deformed bands were identified previously and interpreted as zero- and one-phonon wobbling excitations. As a result of more extensive band search, the level scheme has been considerably extended to include ten new rotational bands and some 630γ-ray transitions. A number of interband linking transitions were revealed, so that all but two bands could be connected with each other. Configurations are proposed for all new bands based on measured observables, with the help of cranked shell model calculations. A γ-ray sequence, previously suggested as a triaxial strongly deformed band based on quasiparticle excitations coexisting with the wobbling excitation in the triaxial potential well, has now been determined to be a signature partner of a coupled band, associated with a normal deformed five-quasiparticle configuration. The possibility of two new bands being associated with triaxial deformation is discussed.

Outlier algorithms are becoming increasingly complex. Thereby, they become much less interpretable to the data scientists applying the algorithms in real-life settings and to end-users using their predictions. We argue that outliers are context-dependent and, therefore, can only be detected via domain knowledge, algorithm insight, and interaction with end-users. As outlier detection is equivalent to unsupervised semantic binary classification, at the core of interpreting an outlier algorithm we find the semantics of the classes, i.e., the algorithm’s conceptual outlier definition. We investigate current interpretable and explainable outlier algorithms: what they are, for whom they are, and what their value proposition is. We then discuss how interpretation and explanation and user involvement have the potential to provide the missing link to bring modern complex outlier algorithms from computer science labs into real-life applications and the challenges they induce.

Predicting which patients will develop adverse reactions to radiotherapy is important for personalised treatment. Prediction will require an algorithm or nomogram combining clinical and biological data. The radiation-induced lymphocyte apoptosis (RILA) assay is the leading candidate as a biological predictor of radiotherapy toxicity. In this study we tested the potential of the assay for standardisation and use in multiple testing laboratories.The assay was standardised and reproducibility determined using samples from healthy volunteers assayed concurrently in three laboratories in Leicester (UK), Mannheim (Germany) and Montpellier (France). RILA assays were performed on samples taken prior to radiotherapy from 1319 cancer patients enrolled in the REQUITE project at multiple centres. The patients were being treated for breast (n = 753), prostate (n = 506) or lung (n = 60) cancer.Inter-laboratory comparisons identified several factors affecting results: storage time, incubation periods and type of foetal calf serum. Following standardisation, there was no significant difference in results between the centres. Significant differences were seen in RILA scores between cancer types (prostate > breast > lung), by smoking status (non-smokers > smokers) and co-morbidity with rheumatoid arthritis (arthritics > non-arthritics).An analysis of acute radiotherapy toxicity showed as expected that RILA assay does not predict most end-points, but unexpectedly did predict acute breast pain. This result may elucidate the mechanism by which the RILA assay predicts late radiotherapy toxicity.The work shows clinical trials involving multiple laboratory measurement of the RILA assay are feasible and the need to account for tumour type and other variables when applying to predictive models.

PurposeFibroblasts are considered to play a major role in the development of fibrotic reaction after radiotherapy and premature radiation-induced differentiation has been proposed as a cellular basis. The purpose was to relate gene expression profiles to radiation-induced phenotypic changes of human skin fibroblasts relevant for radiogenic fibrosis.Materials and MethodsExponentially growing or confluent human skin fibroblast strains were irradiated in vitro with 1–3 fractions of 4 Gy X-rays. The differentiated phenotype was detected by cytomorphological scoring and immunofluorescence microscopy. Microarray analysis was performed on Human Genome U133 plus2.0 microarrays (Affymetrix) with JMP Genomics software, and pathway analysis with Reactome R-package. The expression levels and kinetics of selected genes were validated with quantitative real-time PCR (qPCR) and Western blotting.ResultsIrradiation of exponentially growing fibroblast with 1 × 4 Gy resulted in phenotypic differentiation over a 5-day period. This was accompanied by downregulation of cell cycle-related genes and upregulation of collagen and other extracellular matrix (ECM)-related genes. Pathway analysis confirmed inactivation of proliferation and upregulation of ECM- and glycosaminoglycan (GAG)-related pathways. Furthermore, pathways related to inflammatory reactions were upregulated, and potential induction and signaling mechanisms were identified. Fractionated irradiation (3 × 4 Gy) of confluent cultures according to a previously published protocol for predicting the risk of fibrosis after radiotherapy showed similar downregulation but differences in upregulated genes and pathways.ConclusionGene expression profiles after irradiation of exponentially growing cells were related to radiation-induced differentiation and inflammatory reactions, and potential signaling mechanisms. Upregulated pathways by different irradiation protocols may reflect different aspects of the fibrogenic process thus providing a model system for further hypothesis-based studies of radiation-induced fibrogenesis.