Aarhus University

Background: Bipolar disorder and attention-deficit/hyperactivity disorder are common comorbidities. Attention-deficit/hyperactivity disorder is commonly treated with stimulants (eg, methylphenidate), which, however, have been suggested to cause treatment-emergent mania in patients with bipolar disorder. Here, we assessed the risk of mania, depressive episodes, and psychiatric admissions after initiation of methylphenidate treatment in patients with bipolar disorder. Methods: Using Danish health registries, we identified all individuals registered with a diagnosis of bipolar disorder from January 1, 2000, to January 1, 2018, who were treated with methylphenidate. We applied a 1-year mirror-image model to compare the occurrence of mania, depression, and psychiatric admissions in the period leading up to and after methylphenidate treatment initiation. We furthermore assessed the trend in these outcomes from 4 years before to 1 year after initiation of methylphenidate treatment. Results: A total of 1043 patients with bipolar disorder initiated treatment with methylphenidate. The number of manic episodes decreased by 48% after methylphenidate treatment initiation (P = 0.01), both among patients using mood stabilizers (-50%) and among patients not using mood stabilizers (-45%). The number of manic episodes, however, peaked approximately 6 months before methylphenidate. The results were similar for the secondary outcomes. Conclusions: Initiation of methylphenidate treatment was not associated with an increased risk of mania in patients with bipolar disorder. A decrease in mania, depressive episodes, and psychiatric admissions was observed after methylphenidate. However, these decreases seemed to be driven by regression to the mean after clinical deterioration preceding methylphenidate treatment, rather than by the methylphenidate treatment itself.

The present study assessed for the first time the magnitude and dietary ecological source of total mercury (THg) exposure in a southern population of white-tailed eagles (Haliaeetus albicilla), an apex predator species shown valuable for environmental biomonitoring. This population depends on the Kopački rit Nature Park – the most important breeding sites. We assessed THg exposure, using nestling body feathers collected between 2014–2019 (n = 72), and potential dietary ecological sources, proxied by prey remains and stable isotope analysis. Results show THg concentrations vary significantly over the years, though not showing any time trend. Prey remains analysis shows nests with aquatic prey remains to exhibit higher THg concentrations (median: 7.57 μg g−1 dw; min – max: 6.00–13.16 μg g−1 dw) compared to those with terrestrial remains (median: 3.94 μg g−1 dw; min – max: 0.28–12.04 μg g−1 dw) or evidencing a mixed diet (median: 7.43 μg g−1 dw; min – max: 3.38–12.04 μg g−1 dw). Nests with a predominant aquatic diet show elevated lower δ13C and higher δ15N values, indicating agreement between both dietary approaches. The model selection reveals a combination of year and δ15N best explain the variability in feather THg concentrations. Complementing these predictors with a dietary descriptor based on prey remains results in a poorer model fit and lowered explanatory power, similar to sexing the nestlings. The observed body feather THg concentrations (median: 6.99 μg g−1 dw; min − max: 0.27 − 17.16 μg g−1 dw) exceeded putative biogeochemical background levels (5.00 μg g−1 dw) in 71% of the nestlings, though, did not seem to exceed a threshold at which detrimental physiological effects are expected (40 μg g−1 dw). Continued monitoring is warranted as the studied population is likely exposed to a larger cocktail of contaminants while resident-protected bird areas.

This brief reports a novel low-power 30GHz LNA in 22nm FDSOI CMOS technology. The LNA is based on an active network with CMOS inverting amplifier stages, and input and output feedforward impedance matching networks. It exhibits a peak gain of 11.4 dB, a noise figure of 5.8 dB, with a record power consumption of 0.52 mW from a 0.8 V supply. Owing to its circuit topology, the LNA is compact in size and its core area amounts to 0.20 × 0.22 mm2.

This paper presents an ultrasonically powered micro-system for deep tissue optogenetic stimulation. The developed system is composed of a Base for Powering and Controlling (BPC) and an implantable Dust for optogenetics and drug delivery. The Dust consists of a piezoelectric crystal, a rectifier chip, and a micro-scale custom-designed light-emitting-diode (μLED) integrated, miniaturized, and envisioned to be used for freely moving animal studies. The proposed Dust operates in frequencies up to 5 MHz, power levels in the 0–10 mW range, achieves start-up within 1.8 μs at 2.9 MHz operating frequency at 14.4 mW/mm2 ultrasound power density, and 98.1% chip efficiency at 2 mW input power. With the BPC implemented and attached to (500 μm)3 PZT4 crystals, set to 60 V at 2.8 MHz operating frequency at 3 mm distance in demineralized water, the dust delivered up to 6 mW to its load (μLED for optogenetics), which translates to 0.11% total system efficiency.

This brief reports a compact DC-110GHz single-pole single-throw (SPST) switch in 22nm FDSOI CMOS technology. The switch adopts solely three n-MOSFETs, two of them with a special device option to reduce the substrate parasitic effects, and a third n-MOSFET in parallel to the gate resistance of the series n-MOSFET to improve isolation. Unlike prior wideband mmwave switches, it does not make use of any large passive components, such as spiral inductors, transformers and transmission lines, which are prone to large parasitic effects, including losses, and require large area on silicon. Altogether, the novel switch circuit allows a very compact design, low losses and high isolation performance. The switch exhibits an insertion loss lower than 3.1 dB, an isolation better than 22 dB, and a return loss better than 12 dB, over the entire frequency range from DC to 110 GHz. The area on die amounts to 160 lm2, that is up two or more orders of magnitude smaller than prior wideband mm-wave SPST switches.

Due to developments in European legislation, several halogenated flame retardants are banned due to their toxicity, and the use of phosphor-based flame retardants in plastics is increasing. A revision of ammonium polyphosphate (APP) flame retardant revealed that it is an eye irritant and toxic, thus posing a health issue. Hence APP identification is needed for enabling safe recycling of plastic waste streams. Herein an industrial in-line method for quantitative estimation of APP in low density polyethylene (LDPE) and polypropylene (PP) is demonstrated, by using an industrial hyperspectral imaging system (955 to 1700 nm) and principal component analysis (PCA). Spectra of plastic samples with varying concentrations of APP were applied to build and calibrate a quantitative determination method. PCA and band area ratios (of selected bands) were made and fitted with continuous functions for concentration determination. The plastic samples were characterised by elemental analysis, attenuated total reflection, differential scanning calorimetry, and thermogravimetric analysis. The PCA model outperforms the band area ratio model and predicts APP concentrations between 24.3 and 1.5 wt% in LDPE (R2 = 0.98) and 20.0 and 1.7 wt% in PP (R2 = 0.97). Unknown samples with APP ranging from 23.7 to 2.7 wt% in LDPE and from 18.6 to 2.3 wt% in PP were predicted and correlated to the actual concentrations. The proposed approach is valuable for the plastic recyclers and waste management industries where inline concentration determination of flame retardants is key.

The emission of nitrous oxide (N2O) from agricultural soils to the atmosphere is a significant contributor to anthropogenic greenhouse gas emissions. The recycling of organic nitrogen (N) in manure and crop residues may result in spatiotemporal variability in N2O production and soil efflux which is difficult to capture by process-based models. We propose a multi-species, reactive transport model to provide detailed insight into the spatiotemporal variability in nitrogen (N) transformations around such N2O hotspots, which consists of kinetic reactions of soil respiration, nitrification, nitrifier denitrification, and denitrification represented by a system of coupled partial differential equations. The model was tested with results from an incubation experiment at two different soil moisture levels (−30 and −100 hPa) and was shown to reproduce the recorded N2O and dinitrogen (N2) emissions and the dynamics of important carbon (C) and N components in soil reasonably well. The simulation indicated that the four different microbial populations developed in closely connected but separate layers, with denitrifying bacteria growing within the manure-dominated zone and nitrifying bacteria in the well-aerated soil outside the manure zone and with time also within the manure layer. The modeled N2O production within the manure zone was greatly enhanced by the combined effect of oxygen deficit, abundant carbon source, and supply of nitrogenous substrates. In the wetter soil treatment with a water potential of −30 hPa, the diffusive flux of nitrate (NO3-) across the manure–soil interface was the main source of NO3- for denitrification in the manure zone, while at a soil water potential of −100 hPa, diffusion became less dominant and overtaken by the co-occurrence of nitrification and denitrification in the manure zone. Scenarios were analyzed where the diffusive transport of dissolved organic carbon or different mineral N species was switched off, and they showed that the simultaneous diffusion of NO3-, ammonium (NH4+), and nitrite (NO2-) was crucial to simulate the dynamics of N transformations and N2O emissions in the model. Without considering solute diffusion in process-based N2O models, the rapid turnover of C and N associated with organic hotspots can not be accounted for, and it may result in the underestimation of N2O emissions from soil after manure application. The model and its parameters allow for new detailed insights into the interactions between transport and microbial transformations associated with N2O emissions in heterogeneous soil environments.

Rapid global warming is severely impacting Arctic ecosystems and is predicted to transform the abundance, distribution and genetic diversity of Arctic species, though these linkages are poorly understood. We address this gap in knowledge using palaeogenomics to examine how earlier periods of global warming influenced the genetic diversity of Atlantic walrus (Odobenus rosmarus rosmarus), a species closely associated with sea ice and shallow-water habitats. We analysed 82 ancient and historical Atlantic walrus mitochondrial genomes (mitogenomes), including now-extinct populations in Iceland and the Canadian Maritimes, to reconstruct the Atlantic walrus' response to Arctic deglaciation. Our results demonstrate that the phylogeography and genetic diversity of Atlantic walrus populations was initially shaped by the last glacial maximum (LGM), surviving in distinct glacial refugia, and subsequently expanding rapidly in multiple migration waves during the late Pleistocene and early Holocene. The timing of diversification and establishment of distinct populations corresponds closely with the chronology of the glacial retreat, pointing to a strong link between walrus phylogeography and sea ice. Our results indicate that accelerated ice loss in the modern Arctic may trigger further dispersal events, likely increasing the connectivity of northern stocks while isolating more southerly stocks putatively caught in small pockets of suitable habitat.

Children living with obesity are prevalent worldwide. It is an established finding that many children who start a lifestyle intervention tend to leave prematurely. The aim of this study was to identify characteristics in children with obesity who prematurely leave a lifestyle intervention. The cohort study includes children living with obesity aged 4–17, treated in a Danish family-centered lifestyle intervention between 2014 and 2017. Data were collected from patient records. BMI-SDS was calculated using an external Danish reference population and multivariable regression analysis was used to answer the research question. Of the 159 children included, 64 children who left the intervention within the first 1.5 years were older compared to those who stayed in the intervention (10.2 years ± 2.9 vs 11.5 years ± 3.1, p = 0.005). Older participants (> 66.6th percentile) had a shorter treatment duration (489 days) compared to the youngest (190 days 95% CI: 60; 320, p = 0.005) and middle third (224 days 95% CI: 89; 358, p = 0.001). Additionally, an inverse association was found between duration of treatment and age at baseline (−31 days, 95% CI (−50; −13), p = 0.001). Conclusion: The risk of leaving a lifestyle intervention prematurely was primarily dependent on the age of the participants, emphasizing the importance of including children early in lifestyle interventions. What is Known: • Lifestyle interventions for childhood obesity that are shorter in duration often lead to short-term weight reductions only. Limited knowledge exists on why some children prematurely leave these interventions. What is New: • This study observes a solid inverse correlation and association between age and time spent in the interventions, when treating childhood obesity. We hereby suggest age as an important determinant for the adherence to lifestyle interventions and emphasize the importance of treatment early in life.

This paper investigates the relationship between fine motor skill training in VR, haptic feedback, and physiological arousal. To do so, we present the design and development of a motor skill task (buzzwire), along with a custom vibrotactile feedback attachment for the Geomagic Touch haptic device. A controlled experiment following a between-subjects design was conducted with 73 participants, studying the role of three feedback conditions – visual/kinesthetic, visual/vibrotactile and visual only – on the learning and performance of the considered task and the arousal levels of the participants. Results indicate that performance improved in all three feedback conditions after the considered training session. However, participants reported no change in self-efficacy and in terms of presence and task load (NASA-TLX). All three feedback conditions also showed similar arousal levels. Further analysis revealed that positive changes in performance were linked to higher arousal levels. These results suggest the potential of haptic feedback to affect arousal levels and encourage further research into using this relationship to improve motor skill training in VR.

In this paper we continue the study of two-round broadcast-optimal MPC, where broadcast is used in one of the two rounds, but not in both. We consider the realistic scenario where the round that does not use broadcast is asynchronous. Since a first asynchronous round (even when followed by a round of broadcast) does not admit any secure computation, we introduce a new notion of asynchrony which we call \((t_{d}, t_{m})\)-asynchrony. In this new notion of asynchrony, an adversary can delay or drop up to \(t_{d}\) of a given party’s incoming messages; we refer to \(t_{d}\) as the deafness threshold. Similarly, the adversary can delay or drop up to \(t_{m}\) of a given party’s outgoing messages; we refer to \(t_{m}\) as the muteness threshold. We determine which notions of secure two-round computation are achievable when the first round is \((t_{d}, t_{m})\)-asynchronous, and the second round is over broadcast. Similarly, we determine which notions of secure two-round computation are achievable when the first round is over broadcast, and the second round is (fully) asynchronous. We consider the cases where a PKI is available, when only a CRS is available but private communication in the first round is possible, and the case when only a CRS is available and no private communication is possible before the parties have had a chance to exchange public keys.

The edit distance is a metric widely used in genomics to measure the similarity of two DNA chains. Motivated by privacy concerns, we propose a 2PC protocol to compute the edit distance while preserving the privacy of the inputs. Since the edit distance algorithm can be expressed as a mixed-circuit computation, our approach uses protocols based on secret-sharing schemes like Tinier and SPD\({\mathbb {Z}}_{2^k}\); and also daBits to perform domain conversion and edaBits to perform arithmetic comparisons. We modify the Wagner-Fischer edit distance algorithm, aiming at reducing the number of rounds of the protocol, and achieve a flexible protocol with a trade-off between rounds and multiplications. We implement our proposal in the MP-SPDZ framework, and our experiments show that it reduces the execution time respectively by 81% and 54% for passive and active security with respect to a baseline implementation in a LAN. The experiments also show that our protocol reduces traffic by two orders of magnitude compared to a BMR-MASCOT implementation.

The Green–Griffiths–Lang and Kobayashi hyperbolicity conjectures for generic hypersurfaces of polynomial degree are proved using intersection theory for non-reductive geometric invariant theoretic quotients and recent work of Riedl and Yang.

Let \(H\) be a complex linear algebraic group with internally graded unipotent radical acting on a complex projective variety \(X\). Given an ample linearisation of the action and an associated Fubini–Study Kähler form which is invariant for a maximal compact subgroup \(Q\) of \(H\), we define a notion of moment map for the action of \(H\), and under suitable conditions (that the linearisation is well-adapted and semistability coincides with stability) we describe the (non-reductive) GIT quotient \(X/\!/H\) introduced in (Bérczi et al. in J. Topol. 11(3):826–855, 2018) in terms of this moment map. Using this description we derive formulas for the Betti numbers of \(X/\!/H\) and express the rational cohomology ring of \(X/\!/H\) in terms of the rational cohomology ring of the GIT quotient \(X/\!/T^{H}\), where \(T^{H}\) is a maximal torus in \(H\). We relate intersection pairings on \(X/\!/H\) to intersection pairings on \(X/\!/T^{H}\), obtaining a residue formula for these pairings on \(X/\!/H\) analogous to the residue formula of (Jeffrey and Kirwan in Topology 34(2):291–327, 1995). As an application, we announce a proof of the Green–Griffiths–Lang and Kobayashi conjectures for projective hypersurfaces with polynomial degree.

Aim To systematically review and synthesize findings across qualitative primary studies about fathers' experiences of living with a child with a progressive life‐limiting condition without curative treatment options (C3 conditions). Design Systematic review and metasynthesis. Methods Sandelowski and Barosso's qualitative research methodology guided this review and metasynthesis. A modification of Ricoeur's interpretation theory, described by Lindseth and Norberg, guided the synthesis of qualitative data. The quality of the studies was evaluated using the Joanna Briggs Institute Checklist for Qualitative Research. Data Sources A systematic literature search was conducted on 6 May 2022 and updated on 19 July 2023 on MEDLINE, CINAHL Plus with Full Text, APA PsycInfo and Scopus. Inclusion criteria were English‐written qualitative studies from the year 2000, from which we could extract data on fathers' experiences of living with a child from 0 to 18 years with a progressive life‐limiting condition without curative treatment options. Results Seven reports from Western countries contributed to the review. Through structural analysis, we developed the following themes: ‘Being shattered in the perception of fatherhood’, ‘Establishing a new normal’ and ‘Striving to be acknowledged as a part of the caring team’. Conclusion Fathers had to establish a new normal, and they experienced anticipatory mourning, role conflicts and feeling sidelined in healthcare settings when living with a child with a C3 condition. An important issue for further research on paediatric palliative care (PPC) should be to include fathers in the research sample and report separately on fathers' or mothers' experiences instead of parents' experiences. Impact The findings will be of interest to healthcare personnel and multidisciplinary teams working within PPC, as they give insight into fathers' experiences and suggest interventions to increase healthcare personnel's involvement with fathers, such as telemedicine. Reporting Method Following EQUATOR guidelines, the study was reported according to the enhancing transparency in reporting the synthesis of qualitative research (ENTREQ) framework. Patient or Public Contribution No patient or Public Contribution.

In Gram-negative didermal species of the phylum Bacteroidetes, the majority of pre(pro)proteins exported across the cell membrane via the Sec system follow the Q-rule: a glutamine residue immediately downstream of a leader peptide is exposed as the new amino terminus by type I signal peptidases and converted to a pyroglutamate (also called oxyproline) residue by an inner membrane-associated glutaminyl cyclase (QC). Here, we show that the QC from Porphyromonas gingivalis is essential for growth in laboratory culture conditions. The lethal phenotype of QC deletion could not be rescued by an inactive variant of the enzyme, but it was rescued by QC orthologues from other species, despite their drastically lower activity toward a fluorescent reporter substrate. Replacement of glutamine after the signal peptide by an asparagine residue in selected QC substrates did not affect P. gingivalis viability but reduced the abundance of these proteins. Our data show that glutaminyl cyclization stabilizes P. gingivalis proteins, presumably protecting them from degradation by aminopeptidases. Loss of this protection is tolerated in individual substrates, but the complete loss in all Q-rule substrates is lethal, even in the absence of pressure from a host immune system. IMPORTANCE Exclusively in the Bacteroidetes phylum, most proteins exported across the inner membrane via the Sec system and released into the periplasm by type I signal peptidase have N-terminal glutamine converted to pyroglutamate. The reaction is catalyzed by the periplasmic enzyme glutaminyl cyclase (QC), which is essential for the growth of Porphyromonas gingivalis and other periodontopathogens. Apparently, pyroglutamyl formation stabilizes extracytoplasmic proteins and/or protects them from proteolytic degradation in the periplasm. Given the role of P. gingivalis as the keystone pathogen in periodontitis, P. gingivalis QC is a promising target for the development of drugs to treat and/or prevent this highly prevalent chronic inflammatory disease leading to tooth loss and associated with severe systemic diseases.

Background High parental age is associated with adverse birth and genetic outcomes, but little is known about fecundity in male offspring. Objectives We investigated if high parental age at birth was associated with biomarkers of male fecundity in a large population‐based sample of young men. Materials and methods We conducted a study of 1057 men from the Fetal Programming of Semen Quality (FEPOS) cohort, a sub‐cohort of sons born 1998–2000 into the Danish National Birth Cohort. Semen characteristics and reproductive hormone concentrations were measured in samples provided by the men 2017–2019. Testis volume was determined by self‐measurement. Data on the parental age was drawn from registers. Adjusted relative difference in percentage with 95% confidence intervals were estimated for each outcome according to pre‐specified maternal and paternal age groups (< 30 (reference), 30–34 and ≥ 35) as well as for combinations of parental age groups, using multivariable negative binomial regression models. Results We did not observe consistent associations between parental age and biomarkers of fecundity, although sons of mothers ≥ 35 years had lower sperm concentration (−15% (95% CI: −30, 3)) and total sperm count (−10% (95% CI: −25, 9)). The analysis with parental age combinations showed lower sperm concentration with high age of the parents (both ≥ 35 years: −27%, 95% CI: −40, −19) when compared to the reference where both parents were below 30 years. Discussion and conclusion We found no strong association between higher parental age and biomarkers of fecundity in young men. However, we cannot exclude poorer semen characteristics in sons born by older mothers or with high age of both parents.

The present experience sampling study investigated the effect of age on emotion regulation patterns (i.e., emotion regulation strategy effectiveness, variability, and differentiation) in daily life. The study further explored the implications of potential age differences in emotion regulation patterns for well‐being. A sample of 406 adults (age range: 18–81, 62.8% female) were prompted five times a day for seven days to rate momentary emotions, emotion regulation strategy use, and emotion regulation strategy effectiveness. Based on these ratings, indicators of emotion regulation variability and differentiation were calculated. Well‐being outcomes included daily positive and negative emotions, and symptoms of depression and anxiety assessed at baseline. The findings revealed reduced emotion regulation variability with age and a negative association between emotion regulation variability and well‐being. There were no associations between age and emotion regulation effectiveness or differentiation. Emotion regulation effectiveness was associated with more positive and less negative daily emotions, and these associations were stronger for younger adults compared to older adults. Drawing on prominent lifespan theories, the findings may indicate that as people age, they select and apply a few strategies that they know will be effective given the context and their resources which leads to reduced emotion regulation variability but ultimately more well‐being. Concerning emotion regulation effectiveness, the findings suggest that effectiveness is less important for emotional well‐being in daily life in older adulthood possibly because well‐being is determined by other factors (e.g., less frequent and more predictable stressors) with age.