Halvor Herlyng, Ada J. Ellingsrud, Miroslav Kuchta
et al.
Abstract Cerebrospinal fluid (CSF) is integral to brain function. CSF provides mechanical support for the brain and helps distribute nutrients, neurotransmitters and metabolites throughout the central nervous system. CSF flow is driven by several processes, including the beating of motile cilia located on the walls of the brain ventricles. Despite the physiological importance of CSF, the underlying mechanisms of CSF flow and solute transport in the brain ventricles remain to be comprehensively resolved. This study analyzes and evaluates specifically the role of motile cilia in CSF flow and transport. We developed finite element methods for modeling flow and transport using the geometry of the zebrafish larval brain ventricles, for which we have detailed knowledge of cilia properties and CSF motion. The computational model is validated by in vivo experiments that monitor transport of a photoconvertible protein secreted in the brain ventricles. Our results show that while cilia contribute to advection of large particles, diffusion plays a significant role in the transport of small solutes. We also demonstrate how cilia location and the geometry of the ventricular system impact solute distribution. Altogether, this work presents a computational framework that can be applied to other ventricular systems, together with new concepts of how molecules are transported within the brain and its ventricles.
Joshua Burton, Trine B. Rounge, Trine B. Haugen
et al.
Abstract Testicular germ cell tumour (TGCT) is a malignancy with known inherited risk factors, affecting young men. We have previously identified several hundred differentially abundant circulating RNAs in pre-diagnostic serum from TGCT cases compared to healthy controls. In this study, we performed Weighted Gene Co-expression Network Analysis (WGCNA) on mRNA and miRNA data from these samples. Central genes (hub genes) enriched functional pathways, and regulatory feature prediction were identified for all TGCT subtypes together and according to histology. The TGCT susceptibility genes TEX14, NARS2, and G3BP2, were identified as hub genes in both seminoma and non-seminoma networks. We also identified UBCA1, RCC1, FMR1, OAS3, and UBE2W as hub genes associated with TGCT. The genes OAS3 and UBE2W have previously been associated with testicular dysgenesis. Furthermore, network module analysis indicated transcription factors for oestrogen-related receptors to have a potential role during development of TGCT. The overlap between mRNA network hub genes and TGCT susceptibility genes indicates a common role in TGCT development.
Objective: To determine whether early cognitive function in amyotrophic lateral sclerosis patients predicts future cognitive function and the decision to cease driving.
Design: Observational study.
Subjects: Patients with amyotrophic lateral sclerosis.
Methods: Subjects underwent baseline assessments of cognitive function and driving ability within 4 months of diagnosis, with follow-up evaluation conducted 4 months thereafter. Two hypotheses were tested: (H1) cognitive status remains stable between baseline and follow-up, (H2) patients with baseline cognitive impairment cease driving earlier than those without cognitive changes. Data were analysed using t-tests and regression analysis, with visual inspection of the results.
Results: Of 31 subjects tested at baseline, 5 were under 60 years old, 11 were female, 11 were cognitively impaired, and 61% were driving. Over the 4-month period, cognitive function of the subjects (n = 21) did not change significantly. There was no significant association between baseline cognitive function and follow-up driving status.
Conclusion: Early cognitive function assessment in amyotrophic lateral sclerosis predicts future cognitive function but not currently the decision to cease driving. Cognitive impairment occurs early in the disease, highlighting the importance of early evaluation and implementation of safety measures related to driving.
AbstractBloodstream infections (BSIs) and sepsis are major health problems, annually claiming millions of lives. Traditional blood culture techniques, employed to identify sepsis-causing pathogens and assess antibiotic susceptibility, usually take 2–4 days. Early and accurate antibiotic prescription is vital in sepsis to mitigate mortality and antibiotic resistance. This study aimed to reduce the wait time for sepsis diagnosis by employing shorter blood culture incubation times for BD BACTEC™ bottles using standard laboratory incubators, followed by real-time nanopore sequencing and data analysis. The method was tested on nine blood samples spiked with clinical isolates from the six most prevalent sepsis-causing pathogens. The results showed that pathogen identification was possible at as low as 102–104 CFU/mL, achieved after just 2 h of incubation and within 40 min of nanopore sequencing. Moreover, all the antimicrobial resistance genes were identified at 103–107 CFU/mL, achieved after incubation for 5 h and only 10 min to 3 h of sequencing. Therefore, the total turnaround time from sample collection to the information required for an informed decision on the right antibiotic treatment was between 7 and 9 h. These results hold significant promise for better clinical management of sepsis compared with current culture-based methods.
Gultekin Hasanaliyeva, Ourania Giannakopoulou, Juan Wang
et al.
Modern potato varieties from high-input, conventional farming-focused breeding programs produce substantially (up to 45%) lower yields when grown in organic production systems, and this was shown to be primarily due to less efficient fertilization and late blight (<i>Phytophthora infestans</i>) control methods being used in organic farming. It has been hypothesized that the breeding of potato varieties suitable for the organic/low-input sector should (i) focus on increasing nutrient (especially N) use efficiency, (ii) introduce durable late blight resistance, and (iii) be based on selection under low-input conditions. To test this hypothesis, we used an existing long-term factorial field experiment (the NEFG trials) to assess the effect of crop management practices (rotation design, fertilization regime, and crop protection methods) used in conventional and organic farming systems on crop health, tuber yield, and mineral composition parameters in two potato varieties, Santé and Sarpo mira, that were developed in breeding programs for high and low-input farming systems, respectively. Results showed that, compared to Santé, the variety Sarpo mira was more resistant to foliar and tuber blight but more susceptible to potato scab (<i>Streptomyces scabies</i>) and produced higher yields and tubers with higher concentrations of nutritionally desirable mineral nutrients but lower concentrations of Cd. The study also found that, compared to the Cu-fungicides permitted for late blight control in organic production, application of synthetic chemical fungicides permitted and widely used in conventional production resulted in significantly lower late blight severity in Sante but not in Sarpo mira. Results from both ANOVA and redundancy analysis (RDA) indicate that the effects of climatic (precipitation, radiation, and temperature) and agronomic (fertilization and crop protection) explanatory variables on crop health and yield differed considerably between the two varieties. Specifically, the RDA identified crop protection as a significant driver for Santé but not Sarpo mira, while precipitation was the strongest driver for crop health and yield for Sarpo mira but not Santé. In contrast, the effect of climatic and agronomic drivers on tuber mineral and toxic metal concentrations in the two varieties was found to be similar. Our results support the hypothesis that selection of potato varieties under low agrochemical input conditions can deliver varieties that combine (i) late blight resistance/tolerance, (ii) nutrient use efficiency, and (iii) yield potential in organic farming systems.
Mona Haugum, Mona Haugum, Hilde Hestad Iversen
et al.
IntroductionThe experiences of patients receiving health care constitute an important aspect of health-care quality assessments. One of the purposes of the national program of patient-experience surveys in Norway is to support institutional and departmental improvements to the quality of local health-care services. This program includes national surveys of patients receiving interdisciplinary treatment for substance dependence performed four times between 2013 and 2017. The aims of this study were twofold: (i) to determine the attitudes of employees towards these surveys and their use of the survey results, and (ii) to identify changes in patient experiences at the national level from 2013 to 2017.Material and methodsEmployees were surveyed one week prior to conducting cross-sectional patient experience surveys. One-way ANOVA and chi-square tests were used to assess differences between years, and content analysis was applied to the open-ended comments.ResultsAround 400 employees were recruited in each of the four survey years, and the response rate varied from 61% to 79%. The employees generally reported a positive attitude towards patient-experience surveys, and 40%–50% of them had implemented quality initiatives based on the results of the patient surveys. The mean score for the question on usefulness was higher than 3 (on a Likert scale from 1 to 5 points) for all four surveys. Many employees provided details about the changes that had been made in open-ended comments. The results from the patient-experience surveys demonstrated positive changes over time.DiscussionThe employees had positive viewpoints towards patient-experience surveys, and around half of them had implemented quality initiatives. This implies that employees find such surveys important, and that patient-experience surveys are regarded as useful and actionable. The surveys of patients showed positive changes in their experiences over time. The most-common target areas reported by employees showed clear improvements in patient experiences at the national level.
The pupal stage of “Diamesinae Genus P” Doughman, 1985 is described from specimens collected in northwest Georgia, USA. The pupa is recognized as Diamesinae by dorso- central thoracic setation with no prealar setae and lack of hooklets on tergite II. Also, the anal lobe has apical short tubercles and 3 hooked macrosetae with very distinctive apices. However, leg sheath arrangement differs slightly from described Diamesini with fore and mid leg sheaths directed laterally at the wing apex and frontal setae are lacking, but for now this is considered variation within the tribe. The strikingly unusual larva is recognized as Diamesinae by the annulate third antennal segment as well as characteristics of the premento-hyphoryngeal complex. The larva fits within Diamesini in the most recent keys of Holarctic genera. Currently known distribution, habitat and additional larval morphological details are noted.
This paper will explore two strands of Vilhjálmur Árnason’s extensive body of work: his analysis of dialogue ethics within medical ethics and his analysis of ethics in the Icelandic sagas. The central thesis is that combining these two strands, bioethics and literary analysis, can provide valuable insights to further the discussion of ethics among citizens in multicultural communities.
Vilhjálmur’s1 analysis of the Icelandic sagas shows that the sagas have a specific value foundation, specific virtues as well as narrative in how to present the ethical aspects. In the field of bioethics, he has developed the study of dialogue ethics in several aspects, such as between patient and professional, in interdisciplinary research, and in public deliberation. By integrating insights from historic literary studies with contemporary bioethical research we gain an interesting platform for a discussion on Western assumptions of what constitutes a good dialogue. One of the core aspects in dialogue ethics is how to develop the procedure for a fair, open-minded, and oppression-free discussion in ethical issues. Vilhjálmur’s contributions are summarized here, but could they also be extended beyond the Icelandic and Western horizon?
I will compare his ethical framework to a recent parallel discussion on the claims of indigenous peoples for a fair dialogue. That is, a dialogue that must be inclusive with a carefulness about deciding the foundation of inherent values and the procedure of how to perform the dialogue. Finally, I draw conclusions on what dialogue ethics will gain from this explorative work.
Keywords: dialogue ethics, one health approaches, Indigenous peoples, bioethics, interdisciplinarity, ethics in the Icelandic sagas, medical ethics, literary analysis, multicultural communities
Dennis van der Meer, Weiqiu Cheng, Jaroslav Rokicki
et al.
Abstract Background Schizophrenia is a highly heritable brain disorder with a typical symptom onset in early adulthood. The 2-hit hypothesis posits that schizophrenia results from differential early neurodevelopment, predisposing an individual, followed by a disruption of later brain maturational processes that trigger the onset of symptoms. Study design We applied hierarchical clustering to transcription levels of 345 genes previously linked to schizophrenia, derived from cortical tissue samples from 56 donors across the lifespan. We subsequently calculated clustered-specific polygenic risk scores for 743 individuals with schizophrenia and 743 sex- and age-matched healthy controls. Study results Clustering revealed a set of 183 genes that was significantly upregulated prenatally and downregulated postnatally and 162 genes that showed the opposite pattern. The prenatally upregulated set of genes was functionally annotated to fundamental cell cycle processes, while the postnatally upregulated set was associated with the immune system and neuronal communication. We found an interaction between the 2 scores; higher prenatal polygenic risk showed a stronger association with schizophrenia diagnosis at higher levels of postnatal polygenic risk. Importantly, this finding was replicated in an independent clinical cohort of 3233 individuals. Conclusions We provide genetics-based evidence that schizophrenia is shaped by disruptions of separable biological processes acting at distinct phases of neurodevelopment. The modeling of genetic risk factors that moderate each other’s effect, informed by the timing of their expression, will aid in a better understanding of the development of schizophrenia.
This paper presents a theological critique of divine command theory, a metaethical theory stating that moral wrongness is constituted by God’s command. First, I argue that this theory does not qualify as a Christian moral theory because it lacks connections to central parts of Christian theology, such as Christology. This argument does not imply that the theory is wrong nor that it is inconsistent with Christianity—only that it is not Christian as such. Second, I argue that divine command theory does not fit well with the New Testament’s vision of the moral life, in which being conformed to the image of Christ has primacy over adherence to law. This argument implies that the Christian ethicist should look elsewhere for a metaethical theory. I next argue in favour of a moral theory of imitation, in which the moral life consists of imitating God, the prime exemplar of goodness, which is made possible through an imitation of Christ.
Ana Carolina M F Coêlho, Lara Cioni, Wendy Van Dreunen
et al.
Humans are exposed to perfluoroalkyl acids (PFAA) mainly through direct pathways, such as diet and drinking water, but indirect exposure also occurs when PFAA precursors break down to form legacy PFAA. Exposure to PFAA precursors raises particular concern, as neither the exposure nor the precursors themselves have been well described. In the present study, we aimed to assess the indirect contribution of oxidizable PFAA precursors to the total per- and polyfluoroalkyl substances (PFAS) burden in human plasma following the voluntary phase-out of production of long-chain PFAS. In addition, multiple logistic regression was used to explore associations between selected lifestyle and dietary factors and the oxidizable PFAA precursors fraction. This study included 302 cancer-free participants of the Norwegian Women and Cancer postgenome cohort. PFAS analyses were performed in plasma samples to determine PFAS concentrations before and after oxidation with the Total Oxidizable Precursor (TOP) assay. In pre-TOP analyses, perfluorooctane sulfonic acid (PFOS) was the dominant compound, followed by perfluorooctanoic acid (PFOA).The vast majority (98%) of the study population had increased post-TOP concentrations for at least one PFAA. The formation of PFAA accounted for 12% of the total PFAS burden, with seven PFAA observed post-TOP in at least 30% of study participants. PFHpA, br- PFOA, and PFDA were only detected in post-TOP analyses and showed the highest increase in concentrations. Of the PFAA with increased concentrations, we noted significant associations for year of birth, parity, BMI, and some dietary factors, although they were not consistent between the different PFAA. These results indicate that while the TOP assay might not provide a complete assessment of total PFAS burden in humans, it offers comprehensive assessment of unknown PFAA precursors that might be present in plasma, and it could therefore be implemented as an auxiliary tool in this regard.
Olof Stephansson, Jonas Söderling, Kari Johansson
et al.
Objective To study the association between SARS-CoV-2 infection and newly diagnosed hypertension during pregnancy.Design Prospective, population based cohort study.Setting All singleton pregnancies after 22 completed gestational weeks registered in the Swedish Pregnancy Register and the Medical Birth Registry of Norway, from 1 March 2020 to 24 May 2022.Participants 312 456 individuals available for analysis (201 770 in Sweden and 110 686 in Norway), with pregnancies that reached 42 completed gestational weeks by the end of follow-up in the pregnancy registries, excluding individuals with SARS-CoV-2 infection before pregnancy and those with a diagnosis of pre-existing hypertension or onset of hypertension before 20 gestational weeks.Main outcome measures Newly diagnosed hypertension during pregnancy was defined as a composite outcome of a diagnosis of gestational hypertension, pre-eclampsia, HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome, or eclampsia, from gestational week 20 to one week after delivery. The association between SARS-CoV-2 infection and hypertension during pregnancy was investigated with a stratified Cox proportional hazard model, adjusting for maternal age, body mass index, parity, smoking, region of birth, education, income, coexisting medical conditions, previous hypertension during pregnancy, number of healthcare visits during the past year, and vaccination against SARS-CoV-2. Pre-eclampsia was also analysed as a separate outcome.Results Of 312 456 individuals available for analysis, 8% (n=24 566) had SARS-CoV-2 infection any time during pregnancy, 6% (n=18 051) had a diagnosis of hypertension during pregnancy, and 3% (9899) had pre-eclampsia. SARS-CoV-2 infection during pregnancy was not associated with an increased risk of hypertension during pregnancy (adjusted hazard ratio 0.99, 95% confidence interval 0.93 to 1.04) or pre-eclampsia (0.98, 0.87 to 1.10). The results were similar for SARS-CoV-2 infection in all gestational trimesters and in different time periods that corresponded to dominance of different variants of the SARS-CoV-2 virus.Conclusions This population based study did not find any evidence of an association between SARS-CoV-2 infection during pregnancy and an increased risk of hypertension during pregnancy or pre-eclampsia.
Abbas Mardani, Maryam Maleki, Nasrin Hanifi
et al.
Objective: Despite advances in the diagnosis and treatment of cancer, patients still suffer from the various physical and psychological complications of cancer. The aim of this research was to integrate and synthesize relevant scientific evidence about the effect of lavender on cancer complications. Methods: A systematic review of the international literature was undertaken. The search process encompassed four databases of PubMed [including MEDLINE], Web of Science, Scopus, and Cochrane library without time and language limits. All types of interventional studies examining the effects of lavender on cancer complications were included in data analysis and research synthesis. Relevant data were obtained from eligible studies after quality appraisal using appropriate methodological tools. Given that meta-analysis could not performed, the review findings were synthesized narratively. Results: Thirteen studies were included in this review with a total of 838 patients. Nine studies used a randomized controlled trial design and the majority of them were conducted on patients with multiple types of cancer. Lavender was often used as inhalation aromatherapy. In the majority of the included studies, lavender was significantly effective in the reduction of anxiety and pain, and improved sleep quality and vital signs. Conclusions: This review provides scientific evidence regarding the effectiveness of lavender in mitigating cancer complications. Healthcare providers are suggested to use lavender in patient care along with other healthcare interventions to relieve cancer complications.
ABSTRACT Norwegian welfare and prosperity have thrived in step with a growing petroleum sector dominating Norway's economy. However, new knowledge about the limits of the world's carbon budget and how this might render some fossil fuel reserves ‘unburnable’ now presents carbon as a potential risk. Carbon risk may be climatic, in that petroleum extraction contributes to global greenhouse gas emissions; or it could be economic, as current investments might end up as ‘stranded assets’ in a world seeking to move beyond oil. Since at least 2013, policy advocacy coalitions have employed the carbon risk concept to challenge two fundamental institutions in Norwegian petroleum resource governance: the licensing of offshore exploration areas and the petroleum tax policy. Drawing on official documents and media statements, as well as workshops and interviews with a broad range of stakeholders in Norwegian climate and petroleum policy, this paper analyses policy processes in which notions of carbon risk have been at the centre of disagreements between opposing advocacy coalitions challenging or defending the status quo of Norwegian petroleum resource governance. We identify a growing mismatch between a discernible change in Norwegian public discourse, on the one hand, and inertia in the petroleum resource management regime, on the other. Increased rhetorical connections between carbon risk and petroleum policies have caused tension and debate that challenge the governance of Norwegian petroleum production. Key policy insights Petroleum policy and climate policy have been institutionalized into separate policy fields at the national level in Norway. This separation is increasingly challenged by advocacy coalitions pointing to the climatic and economic risks of future oil and gas production. While the coalition highlighting economic risks has been more successful than the one pointing to climatic risks of oil production, neither has so far had material effects on the practices of Norwegian petroleum governance. The existing international and EU-level climate policy regime helps legitimize a continued separation between climate- and oil policymaking in Norway.
Students at St. Olaf have the opportunity to study a unique subject — Norwegian. St. Olaf is one of a few colleges and universities where students can use Norwegian to complete their foreign language requirement — and beyond the requirement can study in depth the language, literature, culture, and history of Norway. In addition to graduating with a major in Norwegian, St. Olaf students have many opportunities to study and travel in Norway.
Abstract Background and aims While the Nordic countries have considerably stricter controls on opioid prescribing for chronic non-cancer pain than other countries, previous research has warned that prescription of strong opioids is increasing. This study examines consumption of and developments in dispensed prescribed opioids to individuals receiving ambulatory care from 2006 to 2017, using publicly available data from each of three Nordic countries’ national prescription registries. Methods Repeated, cross-sectional design. One-year prevalence of all dispensed prescribed opioids in ATC N02A group were reported for Norway, Denmark, and Sweden in the period 2006–2017 by gender. One-year prevalence of the weak opioids tramadol and codeine and the strong opioid oxycodone were then reported separately over this period for each country. The mean defined daily dose (DDD) per user per year, an estimate of the amount of opioids prescribed, was reported for each of the three opioids in 2016. Results Patterns of dispensed prescribed opioids differ greatly between 2006 and 2017 and between countries, with tramadol increasing in Norway, codeine declining across the board, and oxycodone increasing in all three countries. Norway exceeded Sweden and Denmark in prevalence of all dispensed prescribed opioids, with 12.1% of the female Norwegian population and 9.2% of the male Norwegian population dispensed at least one prescribed opioid as an outpatient in 2016. Norway’s high overall prevalence rates are tempered by dispensing the lowest mean doses of both weak opioids compared to Sweden. Similarly, Sweden dispenses the lowest mean doses of oxycodone but to the largest proportion of its population (3.0%). Conclusions Significant shifts have occurred in the dispensing of prescribed opioids in Norway, Sweden, and Denmark over the past 12 years. The increasing prevalence of oxycodone in all three countries should continue to be monitored. Prescription registries provide a wealth of publicly available data that can be used to monitor and to guide prescribing policies in a more knowledge-based direction.