A century-old tenet in physics and engineering asserts that any type of system, having bandwidth Δω, can interact with a wave over only a constrained time period Δt inversely proportional to the ...bandwidth (Δt·Δω ~ 2π). This law severely limits the generic capabilities of all types of resonant and wave-guiding systems in photonics, cavity quantum electrodynamics and optomechanics, acoustics, continuum mechanics, and atomic and optical physics but is thought to be completely fundamental, arising from basic Fourier reciprocity. We propose that this “fundamental” limit can be overcome in systems where Lorentz reciprocity is broken. As a system becomes more asymmetric in its transport properties, the degree to which the limit can be surpassed becomes greater. By way of example, we theoretically demonstrate how, in an astutely designed magnetized semiconductor heterostructure, the above limit can be exceeded by orders of magnitude by using realistic material parameters. Our findings revise prevailing paradigms for linear, time-invariant resonant systems, challenging the doctrine that high-quality resonances must invariably be narrowband and providing the possibility of developing devices with unprecedentedly high time-bandwidth performance.
Opioid analgesics are powerful pain relievers; however, over time, pain control diminishes as analgesic tolerance develops. The molecular mechanisms initiating tolerance have remained unresolved to ...date. We have previously shown that desensitization of the μ-opioid receptor and interaction with β-arrestins is controlled by carboxyl-terminal phosphorylation. Here we created knockin mice with a series of serine- and threonine-to-alanine mutations that render the receptor increasingly unable to recruit β-arrestins. Desensitization is inhibited in locus coeruleus neurons of mutant mice. Opioid-induced analgesia is strongly enhanced and analgesic tolerance is greatly diminished. Surprisingly, respiratory depression, constipation, and opioid withdrawal signs are unchanged or exacerbated, indicating that β-arrestin recruitment does not contribute to the severity of opioid side effects and, hence, predicting that G-protein-biased µ-agonists are still likely to elicit severe adverse effects. In conclusion, our findings identify carboxyl-terminal multisite phosphorylation as key step that drives acute μ-opioid receptor desensitization and long-term tolerance.
Public trust in immunization is an increasingly important global health issue. Losses in confidence in vaccines and immunization programmes can lead to vaccine reluctance and refusal, risking disease ...outbreaks and challenging immunization goals in high- and low-income settings. National and international immunization stakeholders have called for better monitoring of vaccine confidence to identify emerging concerns before they evolve into vaccine confidence crises.
We perform a large-scale, data-driven study on worldwide attitudes to immunizations. This survey – which we believe represents the largest survey on confidence in immunization to date – examines perceptions of vaccine importance, safety, effectiveness, and religious compatibility among 65,819 individuals across 67 countries. Hierarchical models are employed to probe relationships between individual- and country-level socio-economic factors and vaccine attitudes obtained through the four-question, Likert-scale survey.
Overall sentiment towards vaccinations is positive across all 67 countries, however there is wide variability between countries and across world regions. Vaccine-safety related sentiment is particularly negative in the European region, which has seven of the ten least confident countries, with 41% of respondents in France and 36% of respondents in Bosnia & Herzegovina reporting that they disagree that vaccines are safe (compared to a global average of 13%). The oldest age group (65+) and Roman Catholics (amongst all faiths surveyed) are associated with positive views on vaccine sentiment, while the Western Pacific region reported the highest level of religious incompatibility with vaccines. Countries with high levels of schooling and good access to health services are associated with lower rates of positive sentiment, pointing to an emerging inverse relationship between vaccine sentiments and socio-economic status.
Regular monitoring of vaccine attitudes – coupled with monitoring of local immunization rates – at the national and sub-national levels can identify populations with declining confidence and acceptance. These populations should be prioritized to further investigate the drivers of negative sentiment and to inform appropriate interventions to prevent adverse public health outcomes.
•Overall vaccine confidence is positive, though responses differ between countries.•The European region has the lowest confidence in vaccine safety with France the least confident globally.•Bangladesh, Ecuador, and Iran reported highest agreement that vaccines are important.•Azerbaijan, Russia, and Italy reported most skepticism around vaccine importance.•Education increases confidence in vaccine importance and effectiveness but not safety.
This global survey builds on previous studies of vaccines' perceived importance, safety, effectiveness, and religious compatibility. The worldwide survey investigates attitudes towards vaccines on an unprecedented scale, interviewing 65,819 respondents across 67 countries. This can help inform public health agendas by highlighting national and regional variations in attitudes towards vaccines; for example, that the European region is the least confident region towards vaccine safety. One pattern shared by diverse countries worldwide is a worrying gap between high confidence in vaccine importance yet lower confidence in safety, identifying at-risk countries whose vaccine acceptance may be more precarious than previously thought. Meanwhile, factors such as religion, which past research shows to be crucial in some sub-populations, display no consistent pattern at the global scale, emphasizing the importance for future research of understanding the local drivers of vaccine confidence in more detail.
Sensory issues are highly prevalent in autism and previous findings support a relationship between questionnaires of sensitivity and autistic symptoms and traits, whereas studies that examine this ...relationship through behavioural assessments of sensitivity are less consistent. The current study explores these differences and suggests that behavioural thresholds for sensitivity and subjective sensitivity are distinct constructs. One hundred and eighteen adults completed a visual and auditory detection task and questionnaires on sensory processing and autistic traits. Visual thresholds and subjective visual sensitivity were not correlated, but both were related to autistic traits. Auditory thresholds and subjective auditory sensitivity were also unrelated. Overall, sensitivity is highly associated with autistic traits, however, behavioural and questionnaire assessments lack convergent validity and therefore, likely assess distinct constructs.
Co3O4 nanoparticles were size- and shape-selectively synthesized in a solvothermal approach by the thermal decomposition of either cobalt(II) acetylacetonate Co(acac)2 or cobalt(II) nitrate ...Co(NO3)2 in different solvents followed by calcination under air. Spherical, cubic, octahedral, and platelike nanoparticles with narrow size distributions and sizes ranging from 8 to 90 nm were formed in high yield. The nanoparticles were characterized by X-ray diffraction, scanning and transmission electron microscopy, energy-dispersive X-ray analysis, and X-ray photoelectron spectroscopy. The distinctive influence of the size and shape of the nanoparticles on the electrocatalytic activity in the oxygen evolution reaction is also demonstrated.
This study aims to extend previous research by considering gender differences in borderline personality (BPD) using both dimensional self-reported and clinical measures of symptomatology. Drawing ...from a cross-cultural, clinical trial sample, the authors compared female and male BPD subjects (N = 770; 211 male) between the ages of 18 and 65 using diagnostic and self-report data. The authors found that women with BPD have greater hostility and relationship disruption than men. Gender differences in eating disorders, particularly bulimia, are more divergent than in the general population. Generally, gender differences in BPD in this sample are consistent with known general population differences. Women show greater overall symptomatology, including depressive, anxious, and somatic symptoms. Men have higher rates of antisocial personality disorder and a trend toward higher rates of narcissistic personality disorder. However, several gender differences consistently found in the general population are not present in this BPD sample. There are no differences in aggression, suicidality, substance abuse, panic disorder, or obsessive-compulsive disorder. Gender differences in major depression and posttraumatic stress disorder are attenuated. These findings support the conclusion that BPD may diminish normal gender differences.
Vaccine acceptance depends on public trust and confidence in the safety and efficacy of vaccines and immunization, the health system, healthcare professionals and the wider vaccine research ...community. This systematic review analyses the current breadth and depth of vaccine research literature that explicitly refers to the concept of trust within their stated aims or research questions. After duplicates were removed, 19,643 articles were screened by title and abstract. Of these 2,779 were screened by full text, 35 of which were included in the final analysis. These studies examined a range of trust relationships as they pertain to vaccination, including trust in healthcare professionals, the health system, the government, and friends and family members. Three studies examined generalized trust. Findings indicated that trust is often referred to implicitly (19/35), rather than explicitly examined in the context of a formal definition or discussion of the existing literature on trust in a health context. Within the quantitative research analysed, trust was commonly measured with a single-item measure (9/25). Only two studies used validated multi-item measures of trust. Three studies examined changes in trust, either following an intervention or over the course of a pandemic. The findings of this review indicate a disconnect between the current vaccine hesitancy research and the wider health-related trust literature, a dearth in research on trust in low and middle-income settings, a need for studies on how trust levels change over time and investigations on how resilience to trust-eroding information can be built into a trustworthy health system.
Abstract Stable neuropsychological deficits may provide a reliable basis for identifying etiological subtypes of schizophrenia. The aim of this study was to identify clusters of individuals with ...schizophrenia based on dimensions of neuropsychological performance, and to characterize their neural correlates. We acquired neuropsychological data as well as structural and functional magnetic resonance imaging from 129 patients with schizophrenia and 165 healthy controls. We derived eight cognitive dimensions and subsequently applied a cluster analysis to identify possible schizophrenia subtypes. Analyses suggested the following four cognitive clusters of schizophrenia: (1) Diminished Verbal Fluency, (2) Diminished Verbal Memory and Poor Motor Control, (3) Diminished Face Memory and Slowed Processing, and (4) Diminished Intellectual Function. The clusters were characterized by a specific pattern of structural brain changes in areas such as Wernicke's area, lingual gyrus and occipital face area, and hippocampus as well as differences in working memory-elicited neural activity in several fronto-parietal brain regions. Separable measures of cognitive function appear to provide a method for deriving cognitive subtypes meaningfully related to brain structure and function. Because the present study identified brain-based neural correlates of the cognitive clusters, the proposed groups of individuals with schizophrenia have some external validity.
G protein-coupled receptors (GPCRs) activate G proteins and undergo a complex regulation by interaction with GPCR kinases (GRKs) and the formation of receptor-arrestin complexes. However, the impact ...of individual GRKs on arrestin binding is not clear. We report the creation of eleven combinatorial HEK293 knockout cell clones lacking GRK2/3/5/6, including single, double, triple and the quadruple GRK knockout. Analysis of β-arrestin1/2 interactions for twelve GPCRs in our GRK knockout cells enables the differentiation of two main receptor subsets: GRK2/3-regulated and GRK2/3/5/6-regulated receptors. Furthermore, we identify GPCRs that interact with β-arrestins via the overexpression of specific GRKs even in the absence of agonists. Finally, using GRK knockout cells, PKC inhibitors and β-arrestin mutants, we present evidence for differential receptor-β-arrestin1/2 complex configurations mediated by selective engagement of kinases. We anticipate our GRK knockout platform to facilitate the elucidation of previously unappreciated details of GRK-specific GPCR regulation and β-arrestin complex formation.
Ten C8C1Im+ (1‐methyl‐3‐octylimidazolium)‐based ionic liquids with anions Cl−, Br−, I−, NO3−, BF4−, TfO−, PF6−, Tf2N−, Pf2N−, and FAP− (TfO=trifluoromethylsulfonate, ...Tf2N=bis(trifluoromethylsulfonyl)imide, Pf2N=bis(pentafluoroethylsulfonyl)imide, FAP=tris(pentafluoroethyl)trifluorophosphate) and two C8C1C1Im+ (1,2‐dimethyl‐3‐octylimidazolium)‐based ionic liquids with anions Br− and Tf2N− were investigated by using X‐ray photoelectron spectroscopy (XPS), NMR spectroscopy and theoretical calculations. While 1H NMR spectroscopy is found to probe very specifically the strongest hydrogen‐bond interaction between the hydrogen attached to the C2 position and the anion, a comparative XPS study provides first direct experimental evidence for cation–anion charge‐transfer phenomena in ionic liquids as a function of the ionic liquid’s anion. These charge‐transfer effects are found to be surprisingly similar for C8C1Im+ and C8C1C1Im+ salts of the same anion, which in combination with theoretical calculations leads to the conclusion that hydrogen bonding and charge transfer occur independently from each other, but are both more pronounced for small and more strongly coordinating anions, and are greatly reduced in the case of large and weakly coordinating anions.
Charges in charged systems: Anion and cation interactions in ionic liquids strongly modify the charges on the ions as proven by XPS, NMR spectroscopy and DFT calculations. The smaller, more basic and, thus, more strongly coordinating the anion, the more pronounced the charge transfer to the cation (see graphic). Hydrogen‐bonding‐type interactions between anion and cation do not significantly influence the amount of charge transferred.
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