Associations between effort-reward imbalance and risk of burnout among Swedish physicians.

BACKGROUND: The high prevalence of burnout among Swedish physicians may have several possible effects on individuals and society. However, further investigations of work-related factors associated with the risk of burnout among Swedish physicians are needed. AIMS: We aimed to study the associations between psychosocial work factors, based on the effort-reward imbalance (ERI) model, and the risk of burnout among Swedish physicians. METHODS: A representative sample of 7200 Swedish physicians was invited in 2021. Data were gathered through questionnaires, with a response rate of 41%. Logistic regression models were used to study the associations between exposure to ERI and the risk of burnout. RESULTS: Approximately 62% of Swedish physicians were exposed to a high ERI. Exposure to a high ERI was associated with 11 times increased risk (95% confidence interval 6.5-20.0) of burnout in adjusted models. Large variations in the prevalence of ERI and risk of burnout across sociodemographic and occupational factors were identified, particularly across different clinical specialties. CONCLUSIONS: A majority of Swedish physicians were exposed to high levels of work-related stress, strongly associated with an increased risk of burnout. This population-based cross-sectional study underlines the need to further study variations of work-related stress across clinical specialties and to monitor occupational health among physicians longitudinally.

Observation of Broadband Entanglement in Microwave Radiation from a Single Time-Varying Boundary Condition.

Entangled pairs of microwave photons are commonly produced in the narrow frequency band of a resonator, which represents a modified vacuum density of states. We generate and investigate the entanglement of a stream of photon pairs, generated in a semi-infinite broadband transmission line, terminated by a superconducting quantum interference device (SQUID). A weak pump signal modulates the SQUID inductance, resulting in a single time-varying boundary condition, and we detect all four quadratures of the microwave radiation emitted at two different frequencies separated by 0.7 GHz. Power calibration is done in situ, and we find positive logarithmic negativity and two-mode squeezing below the vacuum in the observed radiation, indicating entanglement.

Tripartite Genuine Non-Gaussian Entanglement in Three-Mode Spontaneous Parametric Down-Conversion.

We show that the states generated by a three-mode spontaneous parametric down-conversion (SPDC) interaction Hamiltonian possess tripartite entanglement of a different nature to other paradigmatic three-mode entangled states generated by the combination of two-mode SPDC interactions. While two-mode SPDC generates Gaussian states whose entanglement can be characterized by standard criteria based on two-mode quantum correlations, these criteria fail to capture the entanglement generated by three-mode SPDC. We use criteria built from three-mode correlation functions to show that the class of states recently generated in a superconducting-circuit implementation of three-mode SPDC ideally have tripartite entanglement, contrary to recent claims in the literature. These criteria are suitable for triple SPDC but we show that they fail to detect tripartite entanglement in other states which are known to possess it, which illustrates the existence of two fundamentally different notions of tripartite entanglement in three-mode continuous-variable systems.

Head trauma in sports - clinical characteristics, epidemiology and biomarkers.

Traumatic brain injury (TBI) is clinically divided into a spectrum of severities, with mild TBI being the least severe form and a frequent occurrence in contact sports, such as ice hockey, American football, rugby, horse riding and boxing. Mild TBI is caused by blunt nonpenetrating head trauma that causes movement of the brain and stretching and tearing of axons, with diffuse axonal injury being a central pathogenic mechanism. Mild TBI is in principle synonymous with concussion; both have similar criteria in which the most important elements are acute alteration or loss of consciousness and/or post-traumatic amnesia following head trauma and no apparent brain changes on standard neuroimaging. Symptoms in mild TBI are highly variable and there are no validated imaging or fluid biomarkers to determine whether or not a patient with a normal computerized tomography scan of the brain has neuronal damage. Mild TBI typically resolves within a few weeks but 10-15% of concussion patients develop postconcussive syndrome. Repetitive mild TBI, which is frequent in contact sports, is a risk factor for a complicated recovery process. This overview paper discusses the relationships between repetitive head impacts in contact sports, mild TBI and chronic neurological symptoms. What are these conditions, how common are they, how are they linked and can they be objectified using imaging or fluid-based biomarkers? It gives an update on the current state of research on these questions with a specific focus on clinical characteristics, epidemiology and biomarkers.

Current and emerging avenues for Alzheimer's disease drug targets.

Alzheimer's disease (AD), the most frequent cause of dementia, is escalating as a global epidemic, and so far, there is neither cure nor treatment to alter its progression. The most important feature of the disease is neuronal death and loss of cognitive functions, caused probably from several pathological processes in the brain. The main neuropathological features of AD are widely described as amyloid beta (Aß) plaques and neurofibrillary tangles of the aggregated protein tau, which contribute to the disease. Nevertheless, AD brains suffer from a variety of alterations in function, such as energy metabolism, inflammation and synaptic activity. The latest decades have seen an explosion of genes and molecules that can be employed as targets aiming to improve brain physiology, which can result in preventive strategies for AD. Moreover, therapeutics using these targets can help AD brains to sustain function during the development of AD pathology. Here, we review broadly recent information for potential targets that can modify AD through diverse pharmacological and nonpharmacological approaches including gene therapy. We propose that AD could be tackled not only using combination therapies including Aß and tau, but also considering insulin and cholesterol metabolism, vascular function, synaptic plasticity, epigenetics, neurovascular junction and blood-brain barrier targets that have been studied recently. We also make a case for the role of gut microbiota in AD. Our hope is to promote the continuing research of diverse targets affecting AD and promote diverse targeting as a near-future strategy.

Observation of the dynamical Casimir effect in a superconducting circuit.

One of the most surprising predictions of modern quantum theory is that the vacuum of space is not empty. In fact, quantum theory predicts that it teems with virtual particles flitting in and out of existence. Although initially a curiosity, it was quickly realized that these vacuum fluctuations had measurable consequences--for instance, producing the Lamb shift of atomic spectra and modifying the magnetic moment of the electron. This type of renormalization due to vacuum fluctuations is now central to our understanding of nature. However, these effects provide indirect evidence for the existence of vacuum fluctuations. From early on, it was discussed whether it might be possible to more directly observe the virtual particles that compose the quantum vacuum. Forty years ago, it was suggested that a mirror undergoing relativistic motion could convert virtual photons into directly observable real photons. The phenomenon, later termed the dynamical Casimir effect, has not been demonstrated previously. Here we observe the dynamical Casimir effect in a superconducting circuit consisting of a coplanar transmission line with a tunable electrical length. The rate of change of the electrical length can be made very fast (a substantial fraction of the speed of light) by modulating the inductance of a superconducting quantum interference device at high frequencies (>10 gigahertz). In addition to observing the creation of real photons, we detect two-mode squeezing in the emitted radiation, which is a signature of the quantum character of the generation process.

Lipid-lowering treatment patterns in patients with new cardiovascular events - estimates from population-based register data in Sweden.

OBJECTIVES: The aim of this study was to assess treatment patterns of lipid-lowering therapy (LLT) in patients with hyperlipidaemia or prior cardiovascular (CV) events who experience new CV events. METHODS: A retrospective population-based cohort study was conducted using Swedish medical records and registers. Patients were included in the study based on a prescription of LLT or CV event history and followed up for up to 7 years for identification of new CV events and assessment of LLT treatment patterns. Patients were stratified into three cohorts based on CV risk level. All outcomes were assessed during the year following index (the date of first new CV event). Adherence was defined as medication possession ratio (MPR) > 0.80. Persistence was defined as no gaps > 60 days in supply of drug used at index. RESULTS: Of patients with major cardiovascular disease (CVD) history (n = 6881), 49% were not on LLT at index. Corresponding data for CV risk equivalent and low/unknown CV risk patients were 37% (n = 3226) and 38% (n = 2497) respectively. MPR for patients on LLT at index was similar across cohorts (0.74-0.75). The proportions of adherent (60-63%) and persistent patients (56-57%) were also similar across cohorts. Dose escalation from dose at index was seen within all cohorts and 2-3% of patients switched to a different LLT after index while 5-6% of patients augmented treatment by adding another LLT. CONCLUSIONS: Almost 50% of patients with major CVD history were not on any LLT, indicating a potential therapeutic gap. Medication adherence and persistence among patients on LLT were suboptimal.

Young adults' views on the relevance of three measures for oral health-related quality of life.

OBJECTIVE: The aim of this study was to explore the views of young adults on the relevance of three measures of oral health-related quality of life (OHRQoL). METHODS: Sixteen young adults aged 21-29 years were interviewed. The selection was strategic with reference to age (21-25 years.; 26-30 years), sex and education (university degree; upper secondary school). The interview guide covered areas on the content and construction of the measures: The Oral Health Impact Profile (OHIP), the Oral Impacts on Daily Performances (OIDP) and the Oral Health-Related Quality of Life UK (OHRQoL-UK). The data were analysed using qualitative content analysis. RESULTS: A theme expressing the latent content was formulated during the data analysis: 'young adults' own experiences were reflected in their views on the OHRQoL measures'; that is, the experiences of young adults of own oral problems and aspects that were found to be especially important for their age group influenced their view on the measures. The self-reported ability to understand and answer the questions varied and the perceived advantages and disadvantages were almost equally distributed among the three measures. CONCLUSIONS: The OHIP, OIDP and OHRQoL-UK were evaluated as being equal by the young adults in this study, with regard both to their pros and cons. The clarity of the measures was regarded as the most important factor, while the length and assessment period were less significant.

Nonequilibrium probing of two-level charge fluctuators using the step response of a single-electron transistor.

We report a new method to study two-level fluctuators (TLFs) by measuring the offset charge induced after applying a sudden step voltage to the gate electrode of a single-electron transistor. The offset charge is measured for more than 20 h for samples made on three different substrates. We find that the offset charge drift follows a logarithmic increase over 4 orders of magnitude in time and that the logarithmic slope increases linearly with the step voltage. The charge drift is independent of temperature, ruling out thermally activated TLFs and demonstrating that the charge fluctuations involve tunneling. These observations are in agreement with expectations for an ensemble of TLFs driven out of equilibrium. From our model, we extract the density of TLFs assuming either a volume density or a surface density.

Dynamical Casimir effect entangles artificial atoms.

We show that the physics underlying the dynamical Casimir effect may generate multipartite quantum correlations. To achieve it, we propose a circuit quantum electrodynamics scenario involving superconducting quantum interference devices, cavities, and superconducting qubits, also called artificial atoms. Our results predict the generation of highly entangled states for two and three superconducting qubits in different geometric configurations with realistic parameters. This proposal paves the way for a scalable method of multipartite entanglement generation in cavity networks through dynamical Casimir physics.

Quantum nondemolition detection of a propagating microwave photon.

The ability to nondestructively detect the presence of a single, traveling photon has been a long-standing goal in optics, with applications in quantum information and measurement. Realizing such a detector is complicated by the fact that photon-photon interactions are typically very weak. At microwave frequencies, very strong effective photon-photon interactions in a waveguide have recently been demonstrated. Here we show how this type of interaction can be used to realize a quantum nondemolition measurement of a single propagating microwave photon. The scheme we propose uses a chain of solid-state three-level systems (transmons) cascaded through circulators which suppress photon backscattering. Our theoretical analysis shows that microwave-photon detection with fidelity around 90% can be realized with existing technologies.

Combination of budesonide/formoterol more effective than fluticasone/salmeterol in preventing exacerbations in chronic obstructive pulmonary disease: the PATHOS study.

OBJECTIVES: Combinations of inhaled corticosteroids (ICSs) and long-acting ß2 -agonists (LABAs) are recommended for patients with moderate and severe chronic obstructive pulmonary disease (COPD). However, it is not known whether different fixed combinations are equally effective. The aim of this study was to investigate exacerbation rates in primary care patients with COPD treated with budesonide/formoterol compared with fluticasone/salmeterol. METHODS: Patients with physician-diagnosed COPD and a record of postdiagnosis treatment with a fixed combination of budesonide/formoterol or fluticasone/salmeterol were included. Data from primary care medical records were linked to those from Swedish national hospital, drug and cause of death registers. Pairwise (1 : 1) propensity score matching was carried out at the index date (first prescription) by prescribed fixed ICS/LABA combination. Exacerbations were defined as hospitalizations, emergency visits and collection of oral steroids or antibiotics for COPD. Yearly event rates were compared using Poisson regression. RESULTS: Matching of 9893 patients (7155 budesonide/formoterol and 2738 fluticasone/salmeterol) yielded two cohorts of 2734 patients, comprising 19 170 patient-years. The exacerbation rates were 0.80 and 1.09 per patient-year in the budesonide/formoterol and fluticasone/salmeterol groups, respectively (difference of 26.6%; P < 0.0001); yearly rates for COPD-related hospitalizations were 0.15 and 0.21, respectively (difference of 29.1%; P < 0.0001). All other healthcare outcomes were also significantly reduced with budesonide/formoterol versus fluticasone/salmeterol. CONCLUSIONS: Long-term treatment with fixed combination budesonide/formoterol was associated with fewer healthcare utilization-defined exacerbations than fluticasone/salmeterol in patients with moderate and severe COPD.

Relativistic quantum teleportation with superconducting circuits.

We study the effects of relativistic motion on quantum teleportation and propose a realizable experiment where our results can be tested. We compute bounds on the optimal fidelity of teleportation when one of the observers undergoes nonuniform motion for a finite time. The upper bound to the optimal fidelity is degraded due to the observer's motion. However, we discuss how this degradation can be corrected. These effects are observable for experimental parameters that are within reach of cutting-edge superconducting technology.

Partial-measurement backaction and nonclassical weak values in a superconducting circuit.

We realize indirect partial measurement of a transmon qubit in circuit quantum electrodynamics by interaction with an ancilla qubit and projective ancilla measurement with a dedicated readout resonator. Accurate control of the interaction and ancilla measurement basis allows tailoring the measurement strength and operator. The tradeoff between measurement strength and qubit backaction is characterized through the distortion of a qubit Rabi oscillation imposed by ancilla measurement in different bases. Combining partial and projective qubit measurements, we provide the solid-state demonstration of the correspondence between a nonclassical weak value and the violation of a Leggett-Garg inequality.

Charge qubit coupled to an intense microwave electromagnetic field in a superconducting Nb device: evidence for photon-assisted quasiparticle tunneling.

We study a superconducting charge qubit coupled to an intensive electromagnetic field and probe changes in the resonance frequency of the formed dressed states. At large driving strengths, exceeding the qubit energy-level splitting, this reveals the well known Landau-Zener-Stückelberg interference structure of a longitudinally driven two-level system. For even stronger drives, we observe a significant change in the Landau-Zener-Stückelberg pattern and contrast. We attribute this to photon-assisted quasiparticle tunneling in the qubit. This results in the recovery of the qubit parity, eliminating effects of quasiparticle poisoning, and leads to an enhanced interferometric response. The interference pattern becomes robust to quasiparticle poisoning and has a good potential for accurate charge sensing.

Associations of HbA1c and educational level with risk of cardiovascular events in 32,871 drug-treated patients with Type 2 diabetes: a cohort study in primary care.

AIMS: To explore the association of HbA1c and educational level with risk of cardiovascular events and mortality in patients with Type 2 diabetes. METHODS: A cohort of 32 871 patients with Type 2 diabetes aged 35 years and older identified by extracting data from electronic patient records for all patients who had a diagnosis of Type 2 diabetes and had glucose-lowering agents prescribed between 1999 and 2009 at 84 primary care centres in Sweden. Associations of mean HbA1c levels and educational level with risks of cardiovascular events and all-cause mortality were analysed. RESULTS: The associations of HbA1c with risk of all-cause and cardiovascular mortality were J-shaped, with the lowest risk observed for cardiovascular mortality at an HbA1c level of 51 mmol/mol (6.8%) for subjects on oral agents and 56 mmol/mol (7.3%) in insulin-treated patients. The lowest risk observed for all-cause mortality was at an HbA1c level of 51 mmol/mol (6.8%) for subjects on oral agents and 56 mmol/mol (7.3%) in insulin-treated patients. There was an increased risk for cardiovascular death [hazard ratio 1.6 (1.2-2.1), P = 0.0008] at the lowest HbA1c decile for subjects in the low education category. For subjects with higher education there was no evident J curve for cardiovascular death [hazard ratio 1.2 (0.8-1.6), P = 0.3873]. CONCLUSIONS: Our results lend support to the recent American Diabetes Association/ European Association for the Study of Diabetes position statement that emphasizes the importance of additional factors, including the propensity for hypoglycaemia, which should influence HbA1c targets and treatment choices for individual patients. (Clinical Trials Registry No; NCT 01121315).

Milrinone and levosimendan during porcine myocardial ischemia -- no effects on calcium overload and metabolism.

BACKGROUND: Although inotropic stimulation is considered harmful in the presence of myocardial ischaemia, both calcium sensitisers and phosphodiesterase inhibitors may offer cardioprotection. We hypothesise that these cardioprotective effects are related to an acute alteration of myocardial metabolism. We studied in vivo effects of milrinone and levosimendan on calcium overload and ischaemic markers using left ventricular microdialysis in pigs with acute myocardial ischaemia. METHODS: Anaesthetised juvenile pigs, average weight 36 kg, were randomised to one of three intravenous treatment groups: milrinone 50 µg/kg bolus plus infusion 0.5 µg/kg/min (n = 7), levosimendan 24 µg/kg plus infusion 0.2 µg/kg/min (n = 7), or placebo (n = 6) for 60 min prior to and during a 45 min acute regional coronary occlusion. Systemic and myocardial haemodynamics were assessed, and microdialysis was performed with catheters positioned in the left ventricular wall. (45) Ca(2+) was included in the microperfusate in order to assess local calcium uptake into myocardial cells. The microdialysate was analysed for glucose, lactate, pyruvate, glycerol, and for (45) Ca(2+) recovery. RESULTS: During ischaemia, there were no differences in microdialysate-measured parameters between control animals and milrinone- or levosimendan-treated groups. In the pre-ischaemic period, arterial blood pressure decreased in all groups while myocardial oxygen consumption remained stable. CONCLUSIONS: These findings reject the hypothesis of an immediate energy-conserving effect of milrinone and levosimendan during acute myocardial ischaemia. On the other hand, the data show that inotropic support with milrinone and levosimendan does not worsen the metabolic parameters that were measured in the ischaemic myocardium.

A four-year clinical and sonographic longitudinal follow-up of clubfeet treated according to Ponseti with normal references.

Purpose: To follow children with a clubfoot by ultrasonography during the entire treatment period up to 4 years and compare with controls. Method: Thirty clubfeet in 20 children treated using the Ponseti method and 29 controls were followed by repeated ultrasonography investigations from neonates to the age of 4 years. The previously established coronal medial and lateral, sagittal dorsal and posterior projections were used. Changes over time, correlations to the Diméglio score, and the course of treatment were studied. Results: The medial malleolus-navicular distance was shorter, while the talar tangent-navicular distance and the talo-navicular angle were larger in clubfeet than in controls even after the initial correction. The healthy feet in unilateral cases did not differ significantly from the controls. The range of motion in the talo-navicular joint was approximately 20° less in clubfeet than in controls during the first four years of life. The medial malleolus-navicular distance (r = -0.58) and the talo-navicular angle (r = 0.66) at the first ultrasonography showed the highest correlation to the number of casts needed to correct the deformities. Conclusion: Ultrasonography can be used to evaluate the initial degree of deformities in clubfeet and to follow the progress of the treatment and growth. Ultrasonography showed a clear difference between clubfeet and controls during the first four years of life. Although it was not possible to define specific limit values as benchmarks in the treatment, dynamic ultrasonography can provide valuable support in the decision-making process when complementary treatment may be needed. Level of evidence: III.

Effects of weathered polyethylene microplastic ingestion on sexual maturation, fecundity and egg quality in maturing broodstock Atlantic cod Gadus morhua.

Microplastics (MPs) have become a global issue as they are omnipresent in the ocean. Fish ingesting MPs through feed could be affected in their physiological function, e.g., disrupted enzyme production and function, reduction of feeding and reproductive failure. This study assessed the effects of feed containing naturally weathered MPs from the Oslofjord (Norway) on the reproductive physiology of Atlantic cod (Gadus morhua). Farmed cod broodstock were fed either control (C-diet) or feeds containing 1% microplastic (MP-diet) starting nine months prior to spawning, from June until May. No major differences were found between diet groups in overall biometrics or gonad histology. Sex steroid levels (testosterone, 11-ketotestosterone and 17ß-estradiol) resulted in expected profiles increasing over time without any significant differences between treatments. Gene expression levels of the steroidogenic enzyme 20ß-hydroxysteroid dehydrogenase (20ß-hsd) and vitellogenin1 (vtg1) showed significant differences between dietary treatments with lower expression in the control group. This can be a direct effect of MPs, but endocrine disrupting effects of potentially leachable plastic additives cannot be completely ruled out. Thus, these enzymes could be indicators of exposure to contaminants that disrupt sexual maturation by affecting the production of primarily maturation-inducing steroid. Although the concentration of MPs employed in this study may not be high enough to elicit any observable short-term biological effects, the observed gene expression suggests that long-term consequences should be considered caused by an expected increase of MPs in marine environments.