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In daycare centres, the close contact of children with other children and employees favours the transmission of infections. The majority of children <6 years attend daycare programmes in Germany, but the role of daycare centres in the SARS-CoV-2 pandemic is unclear. We investigated the transmission risk in daycare centres and the spread of SARS-CoV-2 to associated households. 30 daycare groups with at least one recent laboratory-confirmed SARS-CoV-2 case were enrolled in the study (10/2020–06/2021). Close contact persons within daycare and households were examined over a 12-day period (repeated SARS-CoV-2 PCR tests, genetic sequencing of viruses, symptom diary). Households were interviewed to gain comprehensive information on each outbreak. We determined primary cases for all daycare groups. The number of secondary cases varied considerably between daycare groups. The pooled secondary attack rate (SAR) across all 30 daycare centres was 9.6%. The SAR tended to be higher when the Alpha variant was detected (15.9% vs. 5.1% with evidence of wild type). The household SAR was 53.3%. Exposed daycare children were less likely to get infected with SARS-CoV-2 than employees (7.7% vs. 15.5%). Containment measures in daycare programmes are critical to reduce SARS-CoV-2 transmission, especially to avoid spread to associated households.
In a 1916 paper, Ramanujan studied the additive convolution
of sum-of-divisors functions
, and proved an asymptotic formula for it when a and b are positive odd integers. He also conjectured that his asymptotic formula should hold for all positive real a and b. Ramanujan’s conjecture was subsequently proved by Ingham, and then by Halberstam with a power saving error term.
In this paper, we give a new proof of Ramanujan’s conjecture that obtains lower order terms in the asymptotics for most ranges of the parameters. We also describe a connection to a counting problem in geometric topology that was studied in the second author’s thesis and which served as our initial motivation in studying this sum.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
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.
Nosocomial transmission of influenza is a major concern for infection control. We aimed to dissect transmission dynamics of influenza, including asymptomatic transmission events, in acute care.
Prospective surveillance study during 2 influenza seasons.
Volunteer sample of inpatients on medical wards and healthcare workers (HCWs).
Participants provided daily illness diaries and nasal swabs for influenza A and B detection and whole-genome sequencing for phylogenetic analyses. Contacts between study participants were tracked. Secondary influenza attack rates were calculated based on spatial and temporal proximity and phylogenetic evidence for transmission.
In total, 152 HCWs and 542 inpatients were included; 16 HCWs (10.5%) and 19 inpatients (3.5%) tested positive for influenza on 109 study days. Study participants had symptoms of disease on most of the days they tested positive for influenza (83.1% and 91.9% for HCWs and inpatients, respectively). Also, 11(15.5%) of 71 influenza-positive swabs among HCWs and 3 (7.9%) of 38 influenza-positive swabs among inpatients were collected on days without symptoms; 2 (12.5%) of 16 HCWs and 2 (10.5%) of 19 inpatients remained fully asymptomatic. The secondary attack rate was low: we recorded 1 transmission event over 159 contact days (0.6%) that originated from a symptomatic case. No transmission event occurred in 61 monitored days of contacts with asymptomatic influenza-positive individuals.
Influenza in acute care is common, and individuals regularly shed influenza virus without harboring symptoms. Nevertheless, both symptomatic and asymptomatic transmission events proved rare. We suggest that healthcare-associated influenza prevention strategies that are based on preseason vaccination and barrier precautions for symptomatic individuals seem to be effective.
Psychiatry is facing major challenges during the current coronavirus disease 2019 (COVID)-19 pandemic. These challenges involve its actual and perceived role within the medical system, in particular how psychiatric hospitals can maintain their core mission of attending to people with mental illness while at the same time providing relief to overstretched general medicine services. Although psychiatric disorders comprise the leading cause of the global burden of disease, mental healthcare has been deemphasised in the wake of the onslaught of the pandemic: to make room for emergency care, psychiatric wards have been downsized, clinics closed, psychiatric support systems discontinued and so on. To deal with this pressing issue, we developed a pandemic contingency plan with the aim to contain, decelerate and, preferably, avoid transmission of COVID-19 and to enable and maintain medical healthcare for patients with mental disorders.
To describe our plan as an example of how a psychiatric hospital can share in providing acute care in a healthcare system facing an acute and highly infectious pandemic like COVID-19 and at the same time provide support for people with mental illness, with or without a COVID-19 infection.
This was a descriptive study.
The plan was based on the German national pandemic strategy and several legal recommendations and was implemented step by step on the basis of the local COVID-19 situation. In addition, mid- and long-term plans were developed for coping with the aftermath of the pandemic.
The plan enabled the University Hospital to maintain medical healthcare for patients with mental disorders. It has offered the necessary flexibility to adapt its implementation to the first and second waves of the COVID-19 pandemic in Germany. The plan is designed to serve as an easily adaptable blueprint for psychiatric hospitals around the world.
To assess influenza symptoms, adherence to mask use recommendations, absenteesm and presenteeism in acute care healthcare workers (HCWs) during influenza epidemics.
The TransFLUas influenza transmission study in acute healthcare prospectively followed HCWs prospectively over 2 consecutive influenza seasons. Symptom diaries asking for respiratory symptoms and adherence with mask use recommendations were recorded on a daily basis, and study participants provided midturbinate nasal swabs for influenza testing.
In total, 152 HCWs (65.8% nurses and 13.2% physicians) were included: 89.1% of study participants reported at least 1 influenza symptom during their study season and 77.8% suffered from respiratory symptoms. Also, 28.3% of HCW missed at least 1 working day during the study period: 82.6% of these days were missed because of symptoms of influenza illness. Of all participating HCWs, 67.9% worked with symptoms of influenza infection on 8.8% of study days. On 0.3% of study days, symptomatic HCWs were shedding influenza virus while at work. Among HCWs with respiratory symptoms, 74.1% adhered to the policy to wear a mask at work on 59.1% of days with respiratory symptoms.
Respiratory disease is frequent among HCWs and imposes a significant economic burden on hospitals due to the number of working days lost. Presenteesm with respiratory illness, including influenza, is also frequent and poses a risk for patients and staff.
Maternal periconceptional undernutrition (PCUN) affected fetal pancreatic maturation in late gestation lambs and impaired glucose tolerance in 10-month-old sheep. To examine the importance of the timing of maternal undernutrition around conception, a further cohort was born to PCUN ewes [undernourished for 61 d before conception (PreC), 30 d after conception (PostC), or 61 d before until 30 d after conception (PrePostC)], or normally fed ewes (Control) (n = 15–20/group). We compared glucose tolerance, insulin secretion, and sensitivity at 36 months of age. We also examined protein expression of insulin signalling proteins in muscle from these animals and in muscle from a fetal cohort (132 d of gestation; n = 7–10/group). Adult PostC and PrePostC sheep had higher glucose area under the curve than Controls (P = 0.07 and P = 0.02, respectively), whereas PreC sheep were similar to Controls (P = 0.97). PostC and PrePostC had reduced first-phase insulin secretion compared with Control (P = 0.03 and P = 0.02, respectively). PreC was similar to Control (P = 0.12). Skeletal muscle SLC2A4 protein expression in PostC and PrePostC was increased 19%–58% in fetuses (P = 0.004), but decreased 39%–43% in adult sheep (P = 0.003) compared with Controls. Consistent with this, protein kinase C zeta (PKCζ) protein expression tended to be increased in fetal (P = 0.09) and reduced in adult (P = 0.07) offspring of all PCUN ewes compared with Controls. Maternal PCUN alters several aspects of offspring glucose homeostasis into adulthood. These findings suggest that maternal periconceptional nutrition has a lasting impact on metabolic homeostasis of the offspring.
The COVID-19 pandemic has raised significant concerns for population mental health and the effective provision of mental health services in the light of increased demands and barriers to service delivery . Particular attention is being directed toward the possible neuropsychiatric sequelae of both COVID-19 and of the stringent societal mitigation steps deployed by national governments, concerns that are informed by historical increases in the incidence of psychotic disorders following influenza pandemics . However, so far there has been scant attention paid to other important areas of psychiatry during COVID-19, including medico-legal aspects and human rights. In this paper, we discuss the legal implications for psychiatry of the COVID-19 pandemic and report a novel situation in which psychiatric patients may experience diminution of their statutory protections. We believe that this represents a paradigm shift in psychiatric care and that the consideration of the fundamental rights of psychiatric patients as “less important” than infection control measures compel mental health professionals to “advocate for … patients and their caregivers” in this time of crisis .
Objectives. – Studies on the relation between local cerebral activation and retrieval success usually compared high and low performance conditions, and thus showed performance-related activation of different brain areas. Only a few studies directly compared signal intensities of different response categories during retrieval. During verbal recognition, we recently observed increased parieto-occipital activation related to false alarms. The present study intends to replicate and extend this observation by investigating common and differential activation by veridical and false recognition.
Methods. – Fifteen healthy volunteers performed a verbal recognition paradigm using 160 learned target and 160 new distracter words. The subjects had to indicate whether they had learned the word before or not. Echo-planar MRI of blood-oxygen-level-dependent signal changes was performed during this recognition task. Words were classified post hoc according to the subjects’ responses, i.e. hits, false alarms, correct rejections and misses. Response-related fMRI-analysis was used to compare activation associated with the subjects’ recognition success, i.e. signal intensities related to the presentation of words were compared by the above-mentioned four response types.
Results. – During recognition, all word categories showed increased bilateral activation of the inferior frontal gyrus, the inferior temporal gyrus, the occipital lobe and the brainstem in comparison with the control condition. Hits and false alarms activated several areas including the left medial and lateral parieto-occipital cortex in comparison with subjectively unknown items, i.e. correct rejections and misses. Hits showed more pronounced activation in the medial, false alarms in the lateral parts of the left parieto-occipital cortex.
Conclusions. – Veridical and false recognition show common as well as different areas of cerebral activation in the left parieto-occipital lobe: increased activation of the medial parietal cortex by hits may correspond to true recognition, increased activation of the parieto-occipital cortex by false alarms may correspond to familiarity decisions. Further studies are needed to investigate the reasons for false decisions in healthy subjects and patients with memory problems.
Antenatal exogenous glucocorticoids (ANG) are standard management for women at risk of preterm birth but are reputed to impair glucose tolerance in preterm offspring. We compared lambs born preterm (137 days gestation) following labour induced with exogenous glucocorticoids (G-Prem, glucocorticoid-induced preterm group), or with a progesterone synthesis inhibitor (NG-Prem, non-glucocorticoid-induced preterm group), with term-born lambs (Term; 149 days). We assessed glucose tolerance, insulin secretion and sensitivity at 4 and 10 months n = 11–14/group) and pancreatic and hepatic gene and protein expression at 4 weeks post-term (4 weeks; n = 6/group) and 12 months (12 months; n = 12–13/group). NG-Prem had higher plasma glucose concentrations than G-Prem, but not Term, at 4 months (Mean[SEM] mM: NG-Prem = 4.1[0.1]; G-Prem = 3.4[0.1]; Term = 3.7[0.1]; p = 0.003) and 10 months (NG-Prem = 3.9[0.1]; G-Prem = 3.5[0.1]; Term = 3.7[0.1]; p = 0.01). Insulin sensitivity decreased from 4 to 10 months, in NG-Prem but not in Term (Mean[SEM] µmol·ml−1·kg−1·min−1·ng−1, 4 vs. 10 months: NG-Prem = 18.7[2.5] vs. 9.5[1.5], p < 0.01; Term: 12.1[2.8] vs. 10.4[1.5], p = 0.44). At 12 months, β-cell mass in NG-Prem was reduced by 30% vs. G-Prem (p < 0.01) and 75% vs. Term (p < 0.01) and was accompanied by an increased β-cell apoptosis: proliferation ratio at 12 months. At 12 months, pancreatic glucokinase, igf2 and insulin mRNA levels were reduced 21%–71% in NG-Prem vs. G-Prem and 42%–80% vs. Term. Hepatic glut2 mRNA levels in NG-Prem were 250% of those in G-Prem and Term. Thus, induction of preterm birth without exogenous glucocorticoids more adversely affected pancreas and liver than induction with exogenous glucocorticoids. These findings do not support that ANG lead to long-term adverse metabolic effects, but support an effect of preterm birth itself.
Psychotic disorders are associated with metabolic abnormalities including alterations in glucose and lipid metabolism. A major challenge in the treatment of psychosis is to identify patients with vulnerable metabolic profiles who may be at risk of developing cardiometabolic co-morbidities. It is established that both central and peripheral metabolic organs use lipids to control energy balance and regulate peripheral insulin sensitivity. The endocannabinoid system, implicated in the regulation of glucose and lipid metabolism, has been shown to be dysregulated in psychosis. It is currently unclear how these endocannabinoid abnormalities relate to metabolic changes in psychosis. Here we review recent research in the field of metabolic co-morbidities in psychotic disorders as well as the methods to study them and potential links to the endocannabinoid system. We also describe the bioinformatics platforms developed in the EU project METSY for the investigations of the biological etiology in patients at risk of psychosis and in first episode psychosis patients. The METSY project was established with the aim to identify and evaluate multi-modal peripheral and neuroimaging markers that may be able to predict the onset and prognosis of psychiatric and metabolic symptoms in patients at risk of developing psychosis and first episode psychosis patients. Given the intrinsic complexity and widespread role of lipid metabolism, a systems biology approach which combines molecular, structural and functional neuroimaging methods with detailed metabolic characterisation and multi-variate network analysis is essential in order to identify how lipid dysregulation may contribute to psychotic disorders. A decision support system, integrating clinical, neuropsychological and neuroimaging data, was also developed in order to aid clinical decision making in psychosis. Knowledge of common and specific mechanisms may aid the etiopathogenic understanding of psychotic and metabolic disorders, facilitate early disease detection, aid treatment selection and elucidate new targets for pharmacological treatments.
Barbara Reed, consultant in the fields of records, archives and information management since 1985,
Gillian Oliver, Associate Professor of Information Management and Director of the Centre for Organisational and Social Informatics at Monash University, Australia.,
Frank Upward, archivist, records manager and information manager before accepting a position at Monash University, Australia,
Joanne Evans, Associate Professor, is an ARC Future Fellow in the Faculty of IT at Monash University, Australia
The purpose of this chapter is to provide an introduction to a paradigm shift in ways of thinking about current recordkeeping environments. We begin by explaining recordkeeping informatics, a continuum-based approach to managing authoritative information in the ever shifting, complex and technologically challenging times that confront all of us, including organizations.
We then develop these ideas through a case study of recordkeeping requirements for those who as children experience out-of-home care as a result of child welfare and protection policies. Out-of-home care is the term used in Australia for ‘the care of children and young people up to 18 years who are unable to live with their families, often due to child abuse and neglect. It involves the placement of a child or young person with alternate caregivers on a short- or long-term basis’ (Australian Institute of Family Studies, 2015). These experiences place lifelong identity, memory and accountability needs on the governments and organizations providing these services. Our case study will explore the macro and micro challenges that arise for individuals, organizations, governments and societies as a demonstration of the utility of recordkeeping informatics in designing archival futures in which multiple rights in records are embedded.
The development of recordkeeping informatics has been underway for the past eight years. The original motivation for this work was the need for an up-to-date textbook based on records continuum thinking to support teaching and learning for contemporary recordkeeping. The second edition of Jay Kennedy and Cherryl Schauder's Records Management: a guide to corporate record keeping (1998), is the only title currently in print to fit the bill, but its publication date means that the content, although still valid, is inevitably dated. During our first meeting to discuss the outline of an updated text, it became clear that it would not be possible to address contemporary recordkeeping requirements adequately within the constraints of what had developed as a discipline and occupation in the paper world.
The definition of informatics that we use explains the discipline as ‘the science of information. It studies the representation, processing, and communication of information in natural and artificial systems. Since computers, individuals and organizations all process information, informatics has computational, cognitive and social aspects’ (Fourman, 2003, 237–8).
There are many concerns about the effects of repeated use of glyphosate in glyphosate-resistant (GR) crops, including two that are seemingly contradictory. These are (1) weed escapes and (2) loss of weed diversity. Weeds that escape glyphosate treatment represent species that likely will become troublesome and difficult to control in the future, and identifying these future problems may allow more effective management. In contrast, complete weed control directly reduces the weed component of agroecosystem biodiversity and may lower other components indirectly (e.g., weed-dependent granivores). During 2001 and 2002 effects of glyphosate and conventional weed control treatments on weed community composition and GR soybean yields were studied. Field studies were conducted along a north–south transect of sites spanning a distance of 1600 km from Minnesota to Louisiana. Low-intensity use (single application yr−1) of glyphosate allowed more escapes and maintained higher weed diversity than high-intensity use (two applications yr−1) of glyphosate, and it was equivalent to or even higher than diversity in non-GR systems. Although the same weeds escaped from low- and high-intensity glyphosate treatments, frequency of escapes was higher with less intensive use. These results suggest that limited use of glyphosate would not have profound effects on weed diversity. In addition, crop yield did not differ between GR and non-GR treatments at high latitudes, but below 40° N latitude, with a longer cropping season, yields with low-intensity glyphosate use decreased by about 2% per degree latitude because of competition from escaped weeds.
The perinatal environment has a major influence on long-term health and disease risk. Preterm birth alters early-life environment and is associated with altered metabolic function in adulthood. Whether preterm birth per se or the early nutritional interventions used to support growth in preterm infants underpins this association is unknown. Lambs born preterm, following dexamethasone induction of labour, or spontaneously at term were randomised to receive nutrient supplementation, analogous to the milk fortifier used clinically or water as a control for the first 2 weeks after birth. Thereafter, nutrition was not different between groups. Growth was monitored, and the glucose–insulin axis function was assessed in juvenile (4 months) and adult life (14 months). Early nutrition influenced adult metabolic function and body composition to a greater extent than preterm birth. In supplemented females, arginine-stimulated insulin secretion was increased in preterm but reduced in term-born juveniles compared with controls (repeated-measures ANOVA P<0·01). In supplemented preterm males, adult weight, ponderal index (PI) and fasting insulin concentrations were elevated compared with preterm controls (weight, 75 (sem 3) v. 69 (sem 2) kg; PI, 48·0 (sem 2·1) v. 43·7 (sem 1·7) kg/m3; fasting insulin, 0·19 (sem 0·02) v. 0·10 (sem 0·02) ng/ml). Conversely, supplemented term-born males had reduced adult weight, PI and fasting insulin concentrations compared with term-born controls (weight, 64 (sem 2) v. 70 (sem 2) kg; PI, 44·4 (sem 1·8) v. 48·2 (sem 1·7) kg/m3; fasting insulin, 0·09 (sem 0·02) v. 0·14 (sem 0·02) ng/ml; all group×supplement interactions P<0·05). Adult metabolic health may reflect both gestational age at birth and early nutrition. Human studies are urgently needed to investigate the adult sex-specific health implications of neonatal nutritional strategies.
Preparation of three-dimensionally architectured porous biomaterials can be achieved in a one-step process by stabilizing gelatin with L-lysine diisocyanate ethyl ester (LDI) in water. The reaction of gelatin with LDI in presence of water leads to the formation of oligourea bridges between gelatin molecules and oligourea chains grafted on gelatin. The number and the length of the bridges, as well as of the grafted chains strongly depend on the concentration of the LDI used for the stabilization, and this has huge influence on the mechanical properties of the material on different hierarchical levels. Higher LDI concentrations yield materials with increased deformation resistance in tensile tests due to the higher number of covalent and physical netpoints in the material. However, mechanical properties determined on the micro-level by AFM indentation showed the opposite trend, i.e. a decrease of Young’s modulus with increasing LDI content. This was interpreted by a decreasing number of shorter oligourea bridges between gelatin chains with decreasing LDI content.
Objectives: Health technology reassessment and disinvestment can be difficult due to uncertainties regarding available evidence. Pathology testing to investigate cobalamin (vitamin B12) deficiency is a strong case in point. We conducted a 3-month economic evaluation of five strategies for diagnosing and treating cobalamin deficiency in adult patients hypothetically presenting with new unexplained fatigue in the primary care setting. The first consultation per patient was considered. Screening tests other than serum cobalamin were not included.
Methods: A cost-effectiveness analysis was undertaken using a decision tree to represent the diagnostic / treatment pathways, with relevant cost and utility scores assigned to different stages in the evaluation process. Input parameter values were estimated from published evidence, supplemented by expert opinion, with sensitivity analysis undertaken to represent parameter uncertainty.
Results: Ordering serum vitamin B12 to assess cobalamin deficiency among patients with unexplained fatigue was not cost-effective in any patient population, irrespective of pretest prevalence of this deficiency. For patients with a pretest prevalence above 1 percent, treating all with oral vitamin B12 supplements without testing was most cost-effective, whereas watchful waiting with symptoms monitoring was most cost-effective for patients with lower pretest prevalence probabilities.
Conclusions: Substantial evidence gaps exist for parameter estimation: questionable cobalamin deficiency levels in the fatigued; debatable treatment methods; unknown natural history of the condition. Despite this, we reveal a robust path for disinvestment decision making in the face of a paradox between the evidence required to inform disinvestment compared with its paucity in informing initial funding decisions.
Micromechanical testing of electroplated gold alloy films has been conducted using theta-like specimens. Specimens were formed by a standard combination of photolithography, electroplating, and deep reactive ion etching. Testing was performed using an instrumented indenter and the results interpreted using a finite-element model with a Ramberg–Osgood constitutive law to extract elastic and plastic material properties. The observed results were highly repeatable and appear to be sensitive to variations in both sample dimensions and material properties. These qualities suggest that the testing methodology may have significant value as a quality control technique in the fabrication of metal microelectromechanical systems.
Transistors with 600 V blocking capability and low switching losses are needed for converting one-phase 230 V mains voltage to lower voltage levels in switch-mode power supplies. The transistors operate as a switch and have to block the system voltage with minimized leakage currents in the OFF-state and have to conduct the current in the ON-state with minimized ON-state resistance. Additionally, any switching losses inside the transistor during the transitions in-between OFF and ON-states need to be minimized for efficient power-converting systems. Efficient high-voltage switching using gallium nitride (GaN)-based power transistors requires excellent material properties in the GaN/AlGaN epitaxial layers in conjunction with optimized process modules and device layout. In the example presented here, GaN buffer compositions and device geometry have been optimized to obtain very low vertical and lateral OFF-state leakage currents at 600 V drain bias and to enable a fast device turn-on with only a minor increase in dynamic ON-state resistance. The developed technology was applied to GaN layers grown on SiC and Si substrates to allow a direct comparison of both static and dynamic device parameters. By implementing a p-type GaN gate, normally OFF operation was realized for 70 mΩ/600 V transistors on both substrates. The new GaN-based devices outperform established Si-based superjunction metal oxide semiconductor field-effect transistors in terms of gate charge and switching energy.