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The presence of Global Navigation Satellite System (GNSS) interference poses a significant risk to both GNSS and the infrastructures that depend on them. This article describes how an existing GNSS infrastructure, the Swedish Continuously Operating Reference Stations network SWEPOS with more than 500 stations, can be leveraged to control the quality of GNSS signals and to be able to detect interferences in GNSS and adjacent frequency bands. This study introduces a SWEPOS-based automatic system that effectively detects GNSS interference by examining the signal-to-noise ratio (SNR) of Global Positioning System, Globalnaya Navigatsionnaya Sputnikovaya Sistema, Galileo, and BeiDou frequency bands. By comparing the SNR of tracked satellites against historical data, the system detects radio frequency interference (RFI) by statistically characterizing the SNR of simultaneously tracked satellites. Furthermore, based on the SNR characteristics across satellites, the system distinguishes between RFI and non-RFI sources. The effectiveness of the detection system is demonstrated through both simulated signal interference waves and real-world interference events.

Abstract Single nucleotide polymorphism (SNP) interactions are the key to improving polygenic risk scores. Previous studies reported several significant SNP–SNP interaction pairs that shared a common SNP to form a cluster, but some identified pairs might be false positives. This study aims to identify factors associated with the cluster effect of false positivity and develop strategies to enhance the accuracy of SNP–SNP interactions. The results showed the cluster effect is a major cause of false-positive findings of SNP–SNP interactions. This cluster effect is due to high correlations between a causal pair and null pairs in a cluster. The clusters with a hub SNP with a significant main effect and a large minor allele frequency (MAF) tended to have a higher false-positive rate. In addition, peripheral null SNPs in a cluster with a small MAF tended to enhance false positivity. We also demonstrated that using the modified significance criterion based on the 3 p-value rules and the bootstrap approach (3pRule + bootstrap) can reduce false positivity and maintain high true positivity. In addition, our results also showed that a pair without a significant main effect tends to have weak or no interaction. This study identified the cluster effect and suggested using the 3pRule + bootstrap approach to enhance SNP–SNP interaction detection accuracy.

The increased interest in printed electronics necessitates the development of suitable sustainable substrates for them. In this study, the suitability of acetylated cellulose nanofiber (ACNF) films as substrates for printed electronics were examined through (I) the ink-substrates interaction, (II) print quality, and (III) electrical and (IV) mechanical properties of the printed pattern on the ACNF substrates. The results have been compared with cellulose nanofiber (CNF) and commercial reference material (CRM) substrates. The wetting of the silver nanoparticle (AgNP) ink on the ACNF substrate was found out to be excellent. The thickness of the printed pattern increased and the hole area fraction decreased with each consecutive layer of ink. The comparative investigations demonstrated that the electrical properties of the printed patterns were almost as good for 4 layers of ink on the ACNF substrate (1.6 Ω resistance) as the ones on the CRM substrate (1.2 Ω resistance). Additionally, the printed pattern on the ACNF substrate endured the adhesion and bending tests significantly better compared to the CRM substrate. Therefore, this study demonstrates that ACNF substrates could be a suitable candidate for printed electronics, which are more sustainable yet with similar functionalities in comparison with the conventional fossil based substrates.

Abstract The association of hormonal contraception with increased risk of inflammatory bowel disease (IBD) observed in females suggests involvement of ovarian hormones, such as estradiol, and the estrogen receptors in the progression of intestinal inflammation. Here, we investigated the effects of prophylactic SERM2 and estradiol supplementation in dextran sulfate sodium‐induced colitis using mice with intact ovaries and ovariectomized (OVX) female mice. We found that graded colitis score was threefold reduced in the OVX mice, compared to mice with intact ovaries. Estradiol supplementation, however, aggravated the colitis in OVX mice, increasing the colitis score to a similar level than what was observed in the intact mice. Further, we observed that immune infiltration and gene expression of inflammatory interleukins Il1b, Il6, and Il17a were up to 200‐fold increased in estradiol supplemented OVX colitis mice, while a mild but consistent decrease was observed by SERM2 treatment in intact animals. Additionally, cyclo‐oxygenase 2 induction was increased in the colon of colitis mice, in correlation with increased serum estradiol levels. Measured antagonist properties of SERM2, together with the other results presented here, indicates an exaggerating role of ERα signaling in colitis. Our results contribute to the knowledge of ovarian hormone effects in colitis and encourage further research on the potential use of ER antagonists in the colon, in order to alleviate inflammation.

BackgroundProstate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets.MethodsIn total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry-the Cohort of Swedish Men (COSM) and the ProtecT study. Hazard ratios (HRs) were estimated to compare men with high versus low PHS for association with clinically significant, with any, and with fatal prostate cancer. The impact of genetic risk stratification on the positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was also measured.ResultsThe final model (PHS290) had 290 SNPs with non-zero coefficients. Comparing, for example, the highest and lowest quintiles of PHS290, the hazard ratios (HRs) for clinically significant prostate cancer were 13.73 [95% CI: 12.43-15.16] in ProtecT, 7.07 [6.58-7.60] in African ancestry, 10.31 [9.58-11.11] in Asian ancestry, and 11.18 [10.34-12.09] in COSM. Similar results were seen for association with any and fatal prostate cancer. Without PHS stratification, the PPV of PSA testing for clinically significant prostate cancer in ProtecT was 0.12 (0.11-0.14). For the top 20% and top 5% of PHS290, the PPV of PSA testing was 0.19 (0.15-0.22) and 0.26 (0.19-0.33), respectively.ConclusionsWe demonstrate better genetic risk stratification for clinically significant prostate cancer than prior versions of PHS in multi-ancestry datasets. This is promising for implementing precision-medicine approaches to prostate cancer screening decisions in diverse populations.

This article builds on a classroom study and interviews with facilitators and students on a travelling Folk High School course on global justice and development, an education that raises awareness about colonial history and contemporality. The study explores how the concept of being 'in and against' presents itself in the narratives of the research participants, and what those narratives can say about institutional and global conditions for transnational popular educational engagement. The results mirror the ambiguities of criticising the global, structural, and institutional conditions, while also relying on the same prerequisites, to conduct the course. It shows how working in and against the classroom, as expressed from the different perspectives of the students and the facilitators, entails countering both global and institutional material orders as well as prevailing hegemonic knowledge, and working in and against a gendered, classed, and racialized classroom.

Purpose: The purpose of this study consisted of an organisational development intervention in a growing small and medium-sized enterprises (SME) where the top management's objective was to become an attractive workplace for the next generation of employees. The central problem is how to develop a smart working environment (SWE) based on the needs of this target group. The aim is both practical and theoretical. Design/methodology/approach: The action research (AR) approach was used as a frame for the organisational learning process. The problem identification, targets and activities were developed in an iterative process together with the management team and employees. Starting from the main problem, a methodological plan was outlined for the intervention, including several instruments for collecting both qualitative and quantitative data. AR is an emergent process in which data, researchers and participants are equally contributing in deciding on the next steps to be taken. Findings: The theoretical findings pertain to the definition of what an SWE is in this specific context and how it evolved during the intervention period. It is identified as expansive learning of the concept, which is illustrated through the iterative phases allowing for the expansion of understanding and implementing new ways of being, doing and relating in the organisation. Research limitations/implications: The results are based on a limited and contextually specific sample and are thus descriptive in relation to the organisation subjected to study. Further research is needed to see how the findings are transferable to other contexts. Practical implications: This study highlights how participative approaches and managerial sensitivity to employees' needs are valuable for defining and implementing an SWE and how this approach can improve organisational dynamics and contribute to organisational learning. Originality/value: The study gives insight into factors that the new generation of employees finds most important at work. While prior research on SWE mostly focuses on efficiency and effectiveness framed by digitalisation and workspace, the present findings emphasise the importance of working with the socioemotional dimension at work for ensuring employee sustainability.

Background: Cerebral blood flow (CBF) is believed to be relatively constant within an upper and lower blood pressure limit. Different methods are available to monitor CBF autoregulation during surgery. This study aims to critically analyze the application of the cerebral oxygenation index (COx), one of the commonly used techniques, using a reference to data from a series of clinical registrations. Method: CBF was monitored using near-infrared spectroscopy, while cerebral blood pressure was estimated by recordings obtained from either the radial or femoral artery in 10 patients undergoing cardiopulmonary bypass. The association between CBF and blood pressure was calculated as a moving continuous correlation coefficient. A COx index > 0.4 was regarded as a sign of abnormal cerebral autoregulation (CA). Recordings were examined to discuss reliability measures and clinical feasibility of the measurements, followed by interpretation of individual results, identification of possible pitfalls, and suggestions of alternative methods. Results and Conclusion: Monitoring of CA during cardiopulmonary bypass is intriguing and complex. A series of challenges and limitations should be considered before introducing this method into clinical practice.

Purpose: Learning new vocabulary has been identified as a challenge for students with (developmental) language disorder ((D)LD). In this study, we evaluate the effects of two active learning methods, (a) retrieval practice (RP) and (b) rich vocabulary instruction (RVI), in a group of students with (D)LD in secondary school. Method: A quasi-experimental counterbalanced within-subject design was used to compare and evaluate the effect of RP and RVI on learning Tier 2 vocabulary, with target and control words as dependent measures. Eleven students with (D) LD (M[subscript age] = 14.9 years) attending a language unit participated. RP and RVI were implemented in regular classroom activities during 16 lessons (eight lessons/instructional condition). Learning was assessed by comparing performance on a pretest session 1-2 weeks prior, with posttest performance 1 week after each instructional condition. Results: The learning gain for RP was superior to that for RVI, both with respect to the Bayesian probabilistic estimations for target words relative to control words and in direct comparison with RVI. Only weak evidence was found for RVI with respect to the Bayesian probabilistic estimations for target words relative to control words. Conclusions: All participants showed positive learning gains following RP, whereas the outcome for RVI was more diverse. This initial work suggests that RP promotes larger learning gains relative to RVI and promotes learning across language profiles. This study extends previous studies by exploring the implementation of RP in regular classroom activities and by using more complex to-be-learned material (Tier 2 words).

Abstract Background Polycystin-2 (PC2), encoded by the gene that is mutated in autosomal dominant polycystic kidney disease (ADPKD), functions as a calcium (Ca2+) permeable ion channel. Considerable controversy remains regarding the subcellular localization and signaling function of PC2 in kidney cells. Methods We investigated the subcellular PC2 localization by immunocytochemistry and confocal microscopy in primary cultures of human and rat proximal tubule cells after stimulating cytosolic Ca2+ signaling. Plasma membrane (PM) Ca2+ permeability was evaluated by Fura-2 manganese quenching using time-lapse fluorescence microscopy. Results We demonstrated that PC2 exhibits a dynamic subcellular localization pattern. In unstimulated human or rat proximal tubule cells, PC2 exhibited a cytosolic/reticular distribution. Treatments with agents that in various ways affect the Ca2+ signaling machinery, those being ATP, bradykinin, ionomycin, CPA or thapsigargin, resulted in increased PC2 immunostaining in the PM. Exposing cells to the steroid hormone ouabain, known to trigger Ca2+ oscillations in kidney cells, caused increased PC2 in the PM and increased PM Ca2+ permeability. Intracellular Ca2+ buffering with BAPTA, inositol 1,4,5-trisphosphate receptor (InsP3R) inhibition with 2-aminoethoxydiphenyl borate (2-APB) or Ca2+/Calmodulin-dependent kinase inhibition with KN-93 completely abolished ouabain-stimulated PC2 translocation to the PM. Conclusions These novel findings demonstrate intracellular Ca2+-dependent PC2 trafficking in human and rat kidney cells, which may provide new insight into cyst formations in ADPKD.

BackgroundPolygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46).Materials and method180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy.Results166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer.ConclusionsIncorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.

BACKGROUND: Family history of prostate cancer (PCa) is a well-known risk factor, and both common and rare genetic variants are associated with the disease. OBJECTIVE: To detect new genetic variants associated with PCa, capitalizing on the role of family history and more aggressive PCa. DESIGN, SETTING, AND PARTICIPANTS: A two-stage design was used. In stage one, whole-exome sequencing was used to identify potential risk alleles among affected men with a strong family history of disease or with more aggressive disease (491 cases and 429 controls). Aggressive disease was based on a sum of scores for Gleason score, node status, metastasis, tumor stage, prostate-specific antigen at diagnosis, systemic recurrence, and time to PCa death. Genes identified in stage one were screened in stage two using a custom-capture design in an independent set of 2917 cases and 1899 controls. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Frequencies of genetic variants (singly or jointly in a gene) were compared between cases and controls. RESULTS AND LIMITATIONS: Eleven genes previously reported to be associated with PCa were detected (ATM, BRCA2, HOXB13, FAM111A, EMSY, HNF1B, KLK3, MSMB, PCAT1, PRSS3, and TERT), as well as an additional 10 novel genes (PABPC1, QK1, FAM114A1, MUC6, MYCBP2, RAPGEF4, RNASEH2B, ULK4, XPO7, and THAP3). Of these 10 novel genes, all but PABPC1 and ULK4 were primarily associated with the risk of aggressive PCa. CONCLUSIONS: Our approach demonstrates the advantage of gene sequencing in the search for genetic variants associated with PCa and the benefits of sampling patients with a strong family history of disease or an aggressive form of disease. PATIENT SUMMARY: Multiple genes are associated with prostate cancer (PCa) among men with a strong family history of this disease or among men with an aggressive form of PCa.

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p

Abstract Background Interleukin-18 is a pro-inflammatory cytokine suspected to be associated with atherosclerosis and its complications. We had previously shown that one single nucleotide polymorphism (SNP) of the IL18 gene was associated with cardiovascular disease (CVD) through an interaction with smoking. As a further step for elucidating the contribution of the IL-18 pathway to the etiology of CVD, we here investigated the association between the genetic variability of two IL-18 receptor genes, IL18R1 and IL18RAP, with the risk of developing CVD. Methods Eleven tagging SNPs, 5 in IL18R1 and 6 in IL18RAP, characterizing the haplotypic variability of the corresponding genes; were genotyped in 5 European prospective CVD cohorts including 1416 cases and 1772 non-cases, as part of the MORGAM project. Both single-locus and haplotypes analyses were carried out to investigate the association of these SNPs with CVD. Results We did not find any significant differences in allele, genotype and haplotype frequencies between cases and non-cases for either of the two genes. Moreover, the search for interactions between SNPs located in different genes, including 5 IL18 SNPs previously studied in the MORGAM project, and between SNPs and environmental factors remained unfruitful. Conclusion Our analysis suggests that the variability of IL18R1 and IL18RAP genes are unlikely to contribute to modulate the risk of CVD.

We determined the effect of sample size on performance of polygenic hazard score (PHS) models in prostate cancer. Age and genotypes were obtained for 40,861 men from the PRACTICAL consortium. The dataset included 201,590 SNPs per subject, and was split into training and testing sets. Established-SNP models considered 65 SNPs that had been previously associated with prostate cancer. Discovery-SNP models used stepwise selection to identify new SNPs. The performance of each PHS model was calculated for random sizes of the training set. The performance of a representative Established-SNP model was estimated for random sizes of the testing set. Mean HR98/50 (hazard ratio of top 2% to average in test set) of the Established-SNP model increased from 1.73 [95% CI: 1.69-1.77] to 2.41 [2.40-2.43] when the number of training samples was increased from 1 thousand to 30 thousand. Corresponding HR98/50 of the Discovery-SNP model increased from 1.05 [0.93-1.18] to 2.19 [2.16-2.23]. HR98/50 of a representative Established-SNP model using testing set sample sizes of 0.6 thousand and 6 thousand observations were 1.78 [1.70-1.85] and 1.73 [1.71-1.76], respectively. We estimate that a study population of 20 thousand men is required to develop Discovery-SNP PHS models while 10 thousand men should be sufficient for Established-SNP models.