Aarhus University
  • Aarhus, Denmark
Recent publications
This nationwide cross-sectional study of the lifetime prevalence and determinants of suicide attempts includes 90% of Greenlandic forensic psychiatric patients. Retrospective data were collected from electronic patient files, court documents, and forensic psychiatric assessments using a coding form from a similar study. We used unpaired t-tests and chi2 or Fisher’s exact test. The lifetime prevalence of suicide attempts was 36% (n = 32), and no difference in prevalence was found between male and female patients (p = 0.95). Patients having attempted suicide had a higher rate of physical abuse in childhood (p = 0.04), family history of substance misuse (p = 0.007), and criminal convictions among family members (p = 0.03) than patients who had never attempted suicide. Women primarily used self-poisoning in their latest suicide attempts (67%), whereas men more often used sharp objects or a firearm (42%). Over a third of Greenlandic forensic patients have attempted suicide at some point in their life, and patients with traumatic childhood experiences are at higher risk of suicidal behaviour. It is not possible to conclude whether the lifetime prevalence of suicide attempts among Greenlandic forensic patients is comparable to that of other high-risk groups in other Arctic regions due to methodological differences among the very few other comparable studies.
Background Whiplash injury is common following road traffic crashes affecting millions worldwide, with up to 50% of the injured developing chronic symptoms and 15% having a reduced working capability due to ongoing disability. Many of these patients receive treatment in primary care settings based upon clinical and diagnostic imaging findings. Despite the identification of different types of injuries in the whiplash patients, clinically significant relationships between injuries and chronic symptoms remains to be fully established. This study investigated the feasibility of magnetic resonance imaging (MRI) techniques including quantitative diffusion weighted imaging and measurements of cerebrospinal fluid (CSF) flow as novel non-invasive biomarkers in a population of healthy volunteers and chronic whiplash patients recruited from a chiropractic clinic for the purpose of improving our understanding of whiplash injury. Methods Twenty chronic whiplash patients and 18 healthy age- and gender matched control subjects were included [mean age ± SD (sex ratio; females/males), case group: 37.8 years ± 9.1 (1.22), control group: 35.1 years ± 9.2 (1.25)]. Data was collected from May 2019 to July 2020. Data from questionnaires pertaining to the car crash, acute and current symptoms were retrieved and findings from clinical examination and MRI including morphologic, diffusion weighted and phase-contrast images were recorded. The apparent diffusion coefficient and fractional anisotropy were calculated, and measurement and analysis of CSF flow was conducted. Statistical analyses included Fisher’s exact test, Mann Whitney U test and analysis of variance between groups. Results The studied population was described in detail using readily available clinical tools. No statistically significant differences were found between the groups on MRI. Conclusions This study did not show that MRI‐based measures of morphology, spinal cord and nerve root diffusion or cerebrospinal fluid flow are sensitive biomarkers to distinguish between chronic whiplash patients and healthy controls. The detailed description of the chronic whiplash patients using readily available clinical tools may be of great relevance to the clinician. In the context of feasibility, clinical practice-based advanced imaging studies with a technical setup similar to the presented can be expected to have a high likelihood of successful completion.
Background To assess the achieved risk and benefits of inserting temporary epicardial pacemaker electrodes after open-heart surgery for potential treatment of postoperative cardiac arrhythmias, and to investigate the extent of its use in clinical practice. Main text A systematic search was conducted in PubMed and repeated in Embase and Scopus using the PRISMA guidelines. The search identified 905 studies and resulted in 12 included studies, where the type of surgery, study design, total number of included patients, number of patients having temporary pacemaker electrodes inserted, number of patients requiring temporary pacing, primary reason for pacing, significant factors predicting temporary pacing, registered complications and study conclusion were assessed. Eight papers concluded that routine insertion of temporary pacemaker electrodes in all postoperative patients is unnecessary. One paper concluded that they should always be inserted, while three papers concluded that pacing is useful in the postoperative period, but did not recommend a frequency of which they should be inserted. Conclusions The literature suggests that the subgroup of younger otherwise healthy patients without preoperative arrhythmia having isolated coronary artery bypass grafting surgery or single valve surgery should not routinely have temporary pacemaker electrodes inserted.
The role of the microbiota in human health and disease is well established, including its effects on several cancer types. However, the role of microbial dysbiosis in prostate cancer development, progression, and response to treatment is less well understood. This knowledge gap could perhaps be implicated in the lack of better risk stratification and prognostic tools that incorporate risk factors such as bacterial infections and inflammatory signatures. With over a decade’s research investigating associations between microbiome and prostate carcinogenesis, we are ever closer to finding the crucial biological link between the two. Yet, definitive answers remain elusive, calling for continued research into this field. In this review, we outline the three frequently used NGS based analysis methodologies that are used for microbiome profiling, thereby serving as a quick guide for future microbiome research. We next provide a detailed overview of the current knowledge of the role of the human microbiome in prostate cancer development, progression, and treatment response. Finally, we describe proposed mechanisms of host-microbe interactions that could lead to prostate cancer development, progression or treatment response.
Background Linkage disequilibrium (LD) is commonly measured based on the squared coefficient of correlation $$\left({r}^{2}\right)$$ r 2 between the alleles at two loci that are carried by haplotypes. LD can also be estimated as the $${r}^{2}$$ r 2 between unphased genotype dosage at two loci when the allele frequencies and inbreeding coefficients at both loci are identical for the parental lines. Here, we investigated whether $${r}^{2}$$ r 2 for a crossbred population (F1) can be estimated using genotype data. The parental lines of the crossbred (F1) can be purebred or crossbred. Methods We approached this by first showing that inbreeding coefficients for an F1 crossbred population are negative, and typically differ in size between loci. Then, we proved that the expected $${r}^{2}$$ r 2 computed from unphased genotype data is expected to be identical to the $${r}^{2}$$ r 2 computed from haplotype data for an F1 crossbred population, regardless of the inbreeding coefficients at the two loci. Finally, we investigated the bias and precision of the $${r}^{2}$$ r 2 estimated using unphased genotype versus haplotype data in stochastic simulation. Results Our findings show that estimates of $${r}^{2}$$ r 2 based on haplotype and unphased genotype data are both unbiased for different combinations of allele frequencies, sample sizes (900, 1800, and 2700), and levels of LD. In general, for any allele frequency combination and $${r}^{2}$$ r 2 value scenarios considered, and for both methods to estimate $${r}^{2}$$ r 2 , the precision of the estimates increased, and the bias of the estimates decreased as sample size increased, indicating that both estimators are consistent. For a given scenario, the $${r}^{2}$$ r 2 estimates using haplotype data were more precise and less biased using haplotype data than using unphased genotype data. As sample size increased, the difference in precision and biasedness between the $${r}^{2}$$ r 2 estimates using haplotype data and unphased genotype data decreased. Conclusions Our theoretical derivations showed that estimates of LD between loci based on unphased genotypes and haplotypes in F1 crossbreds have identical expectations. Based on our simulation results, we conclude that the LD for an F1 crossbred population can be accurately estimated from unphased genotype data. The results also apply for other crosses (F2, F3, Fn, BC1, BC2, and BCn), as long as (selected) individuals from the two parental lines mate randomly.
Background Remote Ischemic Conditioning (RIC) has been proposed as a therapeutic intervention to circumvent the ischemia/reperfusion injury (IRI) that is inherent to organ transplantation. Using a porcine kidney transplant model, we aimed to decipher the subclinical molecular effects of a RIC regime, compared to non-RIC controls. Methods Kidney pairs (n = 8 + 8) were extracted from brain dead donor pigs and transplanted in juvenile recipient pigs following a period of cold ischemia. One of the two kidney recipients in each pair was subjected to RIC prior to kidney graft reperfusion, while the other served as non-RIC control. We designed an integrative Omics strategy combining transcriptomics, proteomics, and phosphoproteomics to deduce molecular signatures in kidney tissue that could be attributed to RIC. Results In kidney grafts taken out 10 h after transplantation we detected minimal molecular perturbations following RIC compared to non-RIC at the transcriptome level, which was mirrored at the proteome level. In particular, we noted that RIC resulted in suppression of tissue inflammatory profiles. Furthermore, an accumulation of muscle extracellular matrix assembly proteins in kidney tissues was detected at the protein level, which may be in response to muscle tissue damage and/or fibrosis. However, the majority of these protein changes did not reach significance (p < 0.05). Conclusions Our data identifies subtle molecular phenotypes in porcine kidneys following RIC, and this knowledge could potentially aid optimization of remote ischemic conditioning protocols in renal transplantation.
Background Defacing has become mandatory for anonymization of brain MRI scans; however, concerns regarding data integrity were raised. Thus, we systematically evaluated the effect of different defacing procedures on automated brain atrophy estimation. Methods In total, 268 Alzheimer’s disease patients were included from ADNI, which included unaccelerated ( n = 154), within-session unaccelerated repeat ( n = 67) and accelerated 3D T1 imaging ( n = 114). Atrophy maps were computed using the open-source software veganbagel for every original, unmodified scan and after defacing using afni_refacer, fsl_deface, mri_deface, mri_reface, PyDeface or spm_deface, and the root-mean-square error (RMSE) between z-scores was calculated. RMSE values derived from unaccelerated and unaccelerated repeat imaging served as a benchmark. Outliers were defined as RMSE > 75th percentile and by using Grubbs’s test. Results Benchmark RMSE was 0.28 ± 0.1 (range 0.12–0.58, 75th percentile 0.33). Outliers were found for unaccelerated and accelerated T1 imaging using the 75th percentile cutoff: afni_refacer (unaccelerated: 18, accelerated: 16), fsl_deface (unaccelerated: 4, accelerated: 18), mri_deface (unaccelerated: 0, accelerated: 15), mri_reface (unaccelerated: 0, accelerated: 2) and spm_deface (unaccelerated: 0, accelerated: 7). PyDeface performed best with no outliers (unaccelerated mean RMSE 0.08 ± 0.05, accelerated mean RMSE 0.07 ± 0.05). The following outliers were found according to Grubbs’s test: afni_refacer (unaccelerated: 16, accelerated: 13), fsl_deface (unaccelerated: 10, accelerated: 21), mri_deface (unaccelerated: 7, accelerated: 20), mri_reface (unaccelerated: 7, accelerated: 6), PyDeface (unaccelerated: 5, accelerated: 8) and spm_deface (unaccelerated: 10, accelerated: 12). Conclusion Most defacing approaches have an impact on atrophy estimation, especially in accelerated 3D T1 imaging. Only PyDeface showed good results with negligible impact on atrophy estimation.
Background In livestock breeding, selection for some traits can be improved with direct selection for crossbred performance. However, genetic analyses with phenotypes from crossbred animals require methods for multibreed relationship matrices; especially when some animals are rotationally crossbred. Multiple methods for multibreed relationship matrices exist, but there is a lack of knowledge on how these methods compare for prediction of breeding values with phenotypes from rotationally crossbred animals. Therefore, the objective of this study was to compare models that use different multibreed relationship matrices in terms of ability to predict accurate and unbiased breeding values with phenotypes from two-way rotationally crossbred animals. Methods We compared four methods for multibreed relationship matrices: numerator relationship matrices (NRM), García-Cortés and Toro’s partial relationship matrices (GT), Strandén and Mäntysaari’s approximation to the GT method (SM), and one NRM with metafounders (MF). The methods were compared using simulated data. We simulated two phenotypes; one with and one without dominance effects. Only crossbred animals were phenotyped and only purebred animals were genotyped. Results The MF and GT methods were the most accurate and least biased methods for prediction of breeding values in rotationally crossbred animals. Without genomic information, all methods were almost equally accurate for prediction of breeding values in purebred animals; however, with genomic information, the MF and GT methods were the most accurate. The GT, MF, and SM methods were the least biased methods for prediction of breeding values in purebred animals. Conclusions For prediction of breeding values with phenotypes from rotationally crossbred animals, models using the MF method or the GT method were generally more accurate and less biased than models using the SM method or the NRM method.
This paper investigates how pig housing relates to diversity and circularity of farms and how this influences the capacity of European organic pig producers to cope with economic, legislation, labour and climate-related shocks. It identifies resilience strategies of pig producers in Europe by analysing resilience capacity and attributes to different shocks, namely input and output price shocks, disease outbreaks, climate change, legislation change and labour fluctuations. Based on narratives of 18 pig producers, this paper finds three resilience strategies: an efficiency-based strategy, a nutrient substitution strategy and a farm diversification strategy. Non-resiliency is mostly found among the producers with an all-year outdoor production system following the nutrient substitution strategy related to low feed self-sufficiency. The producers follow an efficiency-based strategy when they cannot accumulate reserves sufficient to cope with shocks. Non-resilience among the farm diversification strategy is related to direct marketing that is labour intensive requires the ability to pay decent wages. To increase the resilience of pig producers in Europe, policies should recognise that these different strategies exist and tailor policies differently for different types of producers.
Objective To evaluate the feasibility of systematic observer training in drug-induced sedation endoscopy (DISE) interpretation. Methods Fifty DISE videos were randomly selected from a group of 200 videos of cohort of patients with OSA and/or snoring. The videos were assessed blindly and independently using a modified VOTE classification by an expert observer and by two novice observers starting their training. A systematic approach was initiated. Clusters of 10 videos were scored individually by each observer and then re-evaluated as the expert observer clarified the decision-making in plenum. Kappa coefficient (κ) was calculated as a measure of agreement. Results The intra-observer variation for the total agreement and kappa values for the expert observer ranged between moderate to substantial agreement in VOTE classification, whereas the novices varied between “less than chance agreement” to “moderate agreement.” The inter-observer variation showed increased agreement and kappa values from day 1 to day 2 for both novice observers except at the velum level for observer C. The total agreement and kappa values for each site also improved compared to results of day 1, except at velum for observer C. The velum site seemed to be more difficult to evaluate. The learning curve varied during the study course for each site of the upper airways. Conclusion This study shows that systematic intensive training is feasible, although expert level is not acquired after 100 evaluations. The learning curve for the expert observer showed “moderate to substantial agreement” but differed between the trainees. Level of evidence 2
Background To investigate if specific sow and piglet behavioral characteristics could be used diagnostically, this case-cohort study of the behavior of sows and piglets during the periparturient period (from 24 h before the birth of first piglet to 24 h after the birth of last piglet) was conducted. Data included 32 sows diagnosed with PDS (PDS+) vs. 37 healthy matched controls (PDS−) and their litters. Results A significant change from active behavior with many postural changes to a more passive behavior was noted in connection with parturition. Sow nesting behavior was less frequent in PDS+ sows compared to PDS− sows during ( p = 0.04) and after parturition ( p = 0.0004). No difference was found between PDS+ and PDS− in the number of postural changes, interval from last time standing to the birth of the first piglet, interval from last time eating/drinking to the birth of the first piglet, interval from the birth of the first piglet to the sow standing after farrowing, interval from the birth of the last piglet until eating/drinking, occurrence of bar biting, or frequency or duration of eating/drinking during the observation period. Piglets of PDS+ sows stayed outside the creep areas more often than piglets of PDS− sows ( p < 0.0001), but there was no difference in the mean number of piglets observed massaging the udder every 10 min. Conclusion These results confirm that sow behavior changes from active before parturition to more passive after parturition. Being diagnosed with PDS affected the periparturient behavior of sows as well as their piglets. The observed reduction in nesting behavior in PDS+ sows may suggest that a highly motivated piglet-oriented behavior was affected. However, classical sickness behaviors like lethargy and passivity seem to be poor markers for PDS.
Background Attention Deficit Hyperactivity Disorder (ADHD) is the most prevalent childhood neurodevelopmental disorder. It shares some genetic risk with Autism Spectrum Disorder (ASD), and the conditions often occur together. Both are potentially associated with abnormal glutamate and GABA neurotransmission, which can be modelled by measuring the synaptic activity in the retina with an electroretinogram (ERG). Reduction of retinal responses in ASD has been reported, but little is known about retinal activity in ADHD. In this study, we compared the light-adapted ERGs of individuals with ADHD, ASD and controls to investigate whether retinal responses differ between these neurodevelopmental conditions. Methods Full field light-adapted ERGs were recorded from 15 ADHD, 57 ASD (without ADHD) and 59 control participants, aged from 5.4 to 27.3 years old. A Troland protocol was used with a random series of nine flash strengths from −0.367 to 1.204 log photopic cd.s.m ⁻² . The time-to-peak and amplitude of the a- and b-waves and the parameters of the Photopic Negative Response (PhNR) were compared amongst the three groups of participants, using generalised estimating equations. Results Statistically significant elevations of the ERG b-wave amplitudes, PhNR responses and faster timings of the b-wave time-to-peak were found in those with ADHD compared with both the control and ASD groups. The greatest elevation in the b-wave amplitudes associated with ADHD were observed at 1.204 log phot cd.s.m ⁻² flash strength ( p < .0001), at which the b-wave amplitude in ASD was significantly lower than that in the controls. Using this measure, ADHD could be distinguished from ASD with an area under the curve of 0.88. Conclusions The ERG b-wave amplitude appears to be a distinctive differential feature for both ADHD and ASD, which produced a reversed pattern of b-wave responses. These findings imply imbalances between glutamate and GABA neurotransmission which primarily regulate the b-wave formation. Abnormalities in the b-wave amplitude could provisionally serve as a biomarker for both neurodevelopmental conditions.
Background Fluid therapy in patients with suspected infection is controversial, and it is not known whether fluid treatment administered in the prehospital setting is beneficial. In the absence of evidence-based guidelines for prehospital fluid therapy for patients with suspected infection, Emergency Medical Services (EMS) personnel are challenged on when and how to initiate such therapy. This study aimed to assess EMS personnel’s decision-making in prehospital fluid therapy, including triggers for initiating fluid and fluid volumes, as well as the need for education and evidence-based guidelines on prehospital fluid therapy in patients with suspected infection. Methods An online survey concerning fluid administration in prehospital patients with suspected infection was distributed to all EMS personnel in the Central Denmark Region, including ambulance clinicians and prehospital critical care anaesthesiologists (PCCA). The survey consisted of sections concerning academic knowledge, statements about fluid administration, triggers to evaluate patient needs for intravenous fluid, and clinical scenarios. Results In total, 468/807 (58%) ambulance clinicians and 106/151 (70%) PCCA responded to the survey. Of the respondents, 73% (n = 341) of the ambulance clinicians and 100% (n = 106) of the PCCA felt confident about administering fluids to prehospital patients with infections. However, both groups primarily based their fluid-related decisions on “clinical intuition”. Ambulance clinicians named the most frequently faced challenges in fluid therapy as “Unsure whether the patient needs fluid” and “Unsure about the volume of fluid the patient needs”. The five most frequently used triggers for evaluating fluid needs were blood pressure, history taking, skin turgor, capillary refill time, and shock index, the last of which only applied to ambulance clinicians. In the scenarios, the majority administered 500 ml to a normotensive woman with suspected sepsis and 1000 ml to a woman with suspected sepsis-related hypotension. Moreover, 97% (n = 250) of the ambulance clinicians strongly agreed or agreed that they were interested in more education about fluid therapy in patients with suspected infection. Conclusion The majority of ambulance clinicians and PCCA based their fluid administration on “clinical intuition”. They faced challenges deciding on fluid volumes and individual fluid needs. Thus, they were eager to learn more and requested research and evidence-based guidelines.
Objective We developed an assay to measure the concentration of 25 hydroxyvitamin D 2 and D 3 in protein extracts derived from stored neonatal dried blood spots. During this study, we postulated that these samples had been contaminated with exogenous vitamin D metabolites because of the addition of bovine serum albumin (BSA) as part of an extraction step undertaken 7 years earlier. The aim of the current study was to develop methods in order to adjust for this contamination. Results We identified between-plate variations in 25 hydroxyvitamin D 2 and D 3 concentrations which suggested the presence of three different BSA batches. Based on repeat extraction (without the addition of BSA) and testing of 395 samples, we developed models to correct for the exogenous 25 hydroxyvitamin D 2 and D 3. The regression models were Diff 25OHD3 = − 8.2 + 1.8* Diff 25OHD2 for low contamination, Diff 25OHD3 = 23.8 + 1.7* Diff 25OHD2 for middle contamination, and Diff 25OHD3 = 14.3 + 3.0* Diff 25OHD2 for high contamination. After these corrections, the three subsamples had comparable distributions within the expected range for both 25 hydroxyvitamin D 2 and D 3 .
Vibration time signals emitted by a defective rolling element bearing are often used to determine its health condition. For real-world measurements these fault signals may be weak compared to the remaining content in the measured signal causing increased difficulties to fault detection. One way of enhancing the fault detection is by demodulation at a filtered frequency band in which the Signal-to-Noise-Ratio (SNR) of the fault signal is high. In the present paper, we propose a method that uses the resonances obtained from Operational Modal Analysis (OMA) as center frequencies for the filter bands as it is assumed that the characteristic bearing fault frequencies modulate resonances or carrier frequencies close to them. An indicator is used to determine which of the resonances from the OMA enhance the fault signal the most and this selection is dependent on the bandwidth as well. The presented method is applied on signals from two experimental cases, an experimental test rig of a planetary gearbox and a wind turbine gearbox, and is compared to the Fast Kurtogram and Log-Cycligram to assess its performance for band selection. The results show that the presented method determines a suited band for band pass filtering which enhances the fault detection at the two complex use cases.
Hybrid vesicles (HVs) assembled from phospholipids and amphiphilic block copolymers (BCPs) are a more recent alternative to liposomes and polymersomes. We aim to change the properties of the HV membranes by varying the chemical composition of the hydrophobic block in the BCPs that have poly(carboxyethyl acrylate) (PCEA) as the hydrophilic part. To this end, statistical copolymers of cholesteryl methacrylate and either butyl methacrylate (BuMA) or 2-hydroxyethyl methacrylate (HEMA) as well as the corresponding homopolymers were synthesized and used as macroinitiator for the extension with PCEA. All the BCPs allowed for the assembly of small and giant HVs with soybean L-α-phosphatidylcholine. The extend of the co-extisting micellar populations varied as shown by transmission electron microscopy and small-angle X-ray spectroscopy. Although the membrane packings derived from spectra when using Laurdan as an environmentally sensitive fluorescent probe were comparable between the different HVs, their permeability towards 5(6)-carboxy-X-rhodamine or carboxyfluorescein depended on the membrane composition, i.e., HEMA-containing membranes had higher permeability than membranes containing the other tested BCPs for small and giant HVs. Further, membranes with BuMA offered the most suitable environment for the association with β-galactosidase illustrated by the efficient substrate conversion. Taken together, the hydrophobic block is a relevant mean to control the morphologies and membrane properties of HVs.
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Anders Lindhardt
  • Department of Engineering
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