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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Background: Continuous electroencephalographic (cEEG) monitoring is essential to diagnosing non-convulsive seizures (NCS), reported to occur in 7-46% of at-risk critically ill patients. However, cEEG is labour-intensive, and given scarcity of resources at most centres cEEG is feasible in only selected patients. We aim to evaluate the clinical utility of cEEG at our centre in order to optimize further cEEG allocation among critically ill patients. Methods: Using a clinical database, we identified critically ill children who underwent cEEG monitoring in 2016, 2017 and 2018. We abstracted underlying diagnoses, indication for cEEG monitoring, cEEG findings, and associated changes in management. Results: Over this three year period, 928 cEEGs were performed. Among the 100 studies analyzed to date, primary indications for monitoring were characterization of events of unclear etiology (32%), diagnosis of NCS (30%), and monitoring of therapy for seizures (17%). Seizures were captured in 31% of patients (22% subclinical only, 5% electroclinical only, 4% both), which resulted in a treatment change in 90% of cases. Non-epileptic events were captured in 26% of patients. Conclusions: cEEG yielded clinically meaningful information in 57% of cases, frequently resulting in management changes. Subgroup analyses by cEEG indication and ICU location will be presented.
Risk populations for HIV infections tend to neglect condom use, making alternative preventive approaches necessary. Accordingly, we modelled the risk of sexual HIV transmission for condom use vs. use of rapid diagnostic test (RDT) systems with subsequent exclusion of potential sexual partners with a correctly or falsely positive test from unprotected sex with and without the use of HIV pre-exposure prophylaxis (PrEP) in a bio-statistical approach. We combined a previously described model of transmission risk for HIV-exposed individuals with a newly suggested model of risk of HIV exposure for sexually active HIV-negative individuals. The model was adapted for several stages of infection and different strategies of HIV infection prevention.
HIV prevention with RDTs can reduce the transmission risk by up to 97% compared with having sex without any prevention and up to 80% compared with condom use. Nevertheless, RDT-based prevention strategies demonstrate a lack of protection in several stages of infection; in particular, RNA-based RDT systems may fail under treatment. RDT-based pre-screening of potential sex partners prior to unprotected sexual contacts substantially reduces HIV transmission risk. Combination of different prevention strategies is advisable for high-risk groups.
This paper gives a bird's-eye view of the various ingredients that make up a modern, model-checking-based approach to performability evaluation: Markov reward models, temporal logics and continuous stochastic logic, model-checking algorithms, bisimulation and the handling of non-determinism. A short historical account as well as a large case study complete this picture. In this way, we show convincingly that the smart combination of performability evaluation with stochastic model-checking techniques, developed over the last decade, provides a powerful and unified method of performability evaluation, thereby combining the advantages of earlier approaches.
To evaluate residual tumour occurrence after vestibular schwannoma surgery, based on intra-operative registration and magnetic resonance imaging one year post-operatively.
Patients undergoing translabyrinthine surgery for vestibular schwannoma in Denmark between 1976 and 2008 were registered in a national database covering 5.5 million inhabitants.
Translabyrinthine surgery was undertaken on 1143 patients. Of these, 978 had total, 140 near-total and 25 subtotal tumour excision, as assessed intra-operatively by the surgeon. One year after surgery, 65 per cent of small tumour remnants and 11 per cent of large tumour remnants were not visible on magnetic resonance imaging. The mean pre-operative size was significantly smaller for totally excised tumours, compared with near-totally and subtotally excised tumours. Revision surgery was performed for 14 patients (1.2 per cent), of whom 2 had received total, 5 near-total and 6 subtotal excisions initially.
Most residual tumours disappear spontaneously, probably due to devascularisation. Few patients with a small residual vestibular schwannoma will require revision surgery or secondary radiotherapy.
Epistasis is an important feature of the genetic architecture of quantitative traits, but the dynamics of epistatic interactions in natural populations and the relationship between epistasis and pleiotropy remain poorly understood. Here, we studied the effects of epistatic modifiers that segregate in a wild-derived Drosophila melanogaster population on the mutational effects of P-element insertions in Semaphorin-5C (Sema-5c) and Calreticulin (Crc), pleiotropic genes that affect olfactory behaviour and startle behaviour and, in the case of Crc, sleep phenotypes. We introduced Canton-S B (CSB) third chromosomes with or without a P-element insertion at the Crc or Sema-5c locus in multiple wild-derived inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and assessed the effects of epistasis on the olfactory response to benzaldehyde and, for Crc, also on sleep. In each case, we found substantial epistasis and significant variation in the magnitude of epistasis. The predominant direction of epistatic effects was to suppress the mutant phenotype. These observations support a previous study on startle behaviour using the same D. melanogaster chromosome substitution lines, which concluded that suppressing epistasis may buffer the effects of new mutations. However, epistatic effects are not correlated among the different phenotypes. Thus, suppressing epistasis appears to be a pervasive general feature of natural populations to protect against the effects of new mutations, but different epistatic interactions modulate different phenotypes affected by mutations at the same pleiotropic gene.
We present the first report of methicillin-resistant Staphylococcus aureus and Propionibacterium acnes parotid abscesses complicated by facial nerve palsy. Facial nerve palsy secondary to parotid gland abscess is rare, with only eight previously reported cases.
Case reports and literature review concerning parotid abscess and facial nerve palsy presentation and management.
Within two months, two female patients presented with parotid gland abscess complicated by unilateral facial paralysis. Both were treated with intravenous antibiotics and surgery. In the first case, methicillin-resistant Staphylococcus aureus was cultivated, in the other, Propionibacterium acnes was found. In the first case, facial nerve function did not recover.
Parotid gland abscess can lead to facial paralysis. Both methicillin-resistant Staphylococcus aureus and Propionibacterium acnes may be involved. Ultrasonography or computed tomography is recommended to exclude a parotid abscess in patients presenting with suppurative parotitis.
To compare three methods of haemostasis used for ‘cold steel’ tonsillectomy, in terms of pain scores and morbidity.
Method and material:
Prospective, randomised, single-blinded, controlled clinical study. Three haemostasis methods were compared: compression of the tonsillar fossae with gauze packs; bipolar diathermy; and local anaesthesia then pack compression. The outcome measures were pain scores (derived from a visual analogue scale), peri-operative bleeding, and post-operative episodes of blood-stained saliva, consultation rate, tonsillar bed healing and days before return to regular diet. One hundred and five patients were included.
Peri-operative bleeding was significantly reduced in the local anaesthesia group compared with the other two groups. Delayed post-operative tonsillar bed healing was noted in the diathermy group. No other significant differences were found between the three haemostasis groups, for any other outcome measures. The presence of blood-stained saliva was associated with higher pain scores.
Diathermy and compression were associated with similar post-tonsillectomy morbidity.
This paper reports on the status of the PHELIX petawatt laser which is
built at the Gesellschaft fuer Schwerionenforschung (GSI) in close
collaboration with the Lawrence Livermore National Laboratory (LLNL), and
the Commissariat à l'Energie Atomique (CEA) in France. First
experiments carried out with the chirped pulse amplification (CPA)
front-end will also be briefly reviewed.
One promising route to integrate nanostructured titania (NST) into nano/micro electrical mechanical systems (N/MEMS) devices is by reacting Ti films with aqueous hydrogen peroxide (aq. H2O2) solution. However, little is known about the reaction kinetics between aq. H2O2 and Ti thin films. Here, the effect of Ti microstructure and film thickness on kinetics of reaction was investigated. For films less than 50 nm thick, the kinetics is interface-reaction controlled. For thicker films, the reaction is controlled by diffusion through a hydrated titania gel layer. Activation energies of these kinetics were extracted. Pore size of NST is affected by thickness of parent Ti films. Depending on thickness of parent Ti films, NST with average pore sizes ranging from 15 nm to 150 nm was formed. The ability to form integrated porous NST features with controllable pore sizes may have implications on the development of devices for drug delivery and macromolecular separation.
Long and fine Zn1-xCdxSe pseudo-binary alloy nanowires of various compositions x covering the entire range were grown by metalorganic chemical vapor deposition, using diethlyzinc, dimethylcadmium and diisopropylselenide as precursors, on Si (100) and GaAs (100) substrates; sputtered gold was used as a catalyst to promote nanowire formation. By controlling the ratio of the flows of the precursors, the temperature and the pressure during growth, we obtained nanowires of desired compositions. The morphology, structure and optical properties of the nanowires were studied by various techniques, including secondary electron microscopy, atomic force microscopy, transmission electron microscopy, X-ray diffraction, photoluminescence, and Raman scattering. Depending on the substrate, composition and conditions of growth, either the zincblende or wurtzite nanowires were obtained. At compositions where the stable form would have been normally wurtzite, the zincblende form could be obtained under certain growth conditions. From the orientations of the ordered nanowires on the substrate surface, their directions of growth were deduced and confirmed by high resolution lattice imaging. The relationship between the band gap and the composition of the nanowires were measured and found to deviate from that of bulk alloys and epilayers. The interplay between the growth conditions and compositions and morphology of the nanowires are discussed.
In this paper we report the experimental results that polymer micro-emulsions (up to 10 wt%) behave like Newtonian liquids in ultrasound-modulated two-fluid (UMTF) atomization. Specifically, the emulsion drops generated are much smaller and more narrowly sized than those generated in conventional ultrasonic atomization (without air). After spray drying, the PMMA emulsion drops yield uniform nanoparticles that were originally dispersed in the micro-emulsion. Contrary to the conventional view that viscoelastic liquids are more difficult to atomize than Newtonian liquids, we found that ultrasound enhanced atomization of viscoelastic liquids such as gel-forming xanthan gum solutions. Under similar aerodynamic conditions using UMTF atomization at 54 kHz, 40-μm-diameter uniform drops were obtained for Xan solutions, but not for Newtonian aqueous glycerol of same viscosity.