There is considerable interest in the role of neuroimmune processes in neuropsychiatric presentations among young people seeking mental health, neurological, paediatric and rheumatological services. The increasing availability of new immunotherapies, particularly monoclonal antibodies, introduces challenges in effectively and appropriately selecting candidates for immunotherapies. Neuroimmune-mediated neuropsychiatric syndromes (NIMNPS) typically include two broad types: i) ‘autoimmune encephalitis’, characterised by acute or subacute onset, neurological signs such as seizures, delirium or motor features and severe psychotic or major mood phenomena. Anti-N-methyl-D-aspartate receptor encephalitis was a pioneering clinical example, but various other autoantibodies have since been associated with this phenotype; and ii) atypical mood or psychotic syndromes with sub-acute or insidious onset, moderately severe atypical mood or psychotic symptoms, autonomic dysregulation, narcolepsy-like features, poor response to conventional treatments and adverse (notably motor) effects from psychotropic medications. Diagnosis of NIMNPS requires clinical or laboratory evidence of direct brain involvement, though autoantibodies are not always detectable. Given the broad and controversial diagnostic criteria for NIMNPS, we propose standardised clinical criteria for identifying ‘possible cases’, followed by laboratory, neuropsychological and brain imaging tests to confirm ‘probable’ cases suitable for immunotherapy. We emphasise rapid clinical and informed co-decision-making with young people and their families and loved ones. While immunotherapy holds promise for symptom alleviation, highly-personalised approaches and long-term management are essential. Future research should validate our proposed criteria, establish optimal, standardised yet personalised immunotherapy strategies that balance between clinical benefit and risks, and identify predictive markers of treatment response.

Female fertility is a complex trait with age-specific changes in spontaneous dizygotic (DZ) twinning and fertility. To elucidate factors regulating female fertility and infertility, we conducted a genome-wide association study (GWAS) on mothers of spontaneous DZ twins (MoDZT) versus controls (3273 cases, 24,009 controls). This is a follow-up study to the Australia/New Zealand (ANZ) component of that previously reported (Mbarek et al., 2016), with a sample size almost twice that of the entire discovery sample meta-analysed in the previous article (and five times the ANZ contribution to that), resulting from newly available additional genotyping and representing a significant increase in power. We compare analyses with and without male controls and show unequivocally that it is better to include male controls who have been screened for recent family history, than to use only female controls. Results from the SNP based GWAS identified four genomewide significant signals, including one novel region, ZFPM1 (Zinc Finger Protein, FOG Family Member 1), on chromosome 16. Previous signals near FSHB (Follicle Stimulating Hormone beta subunit) and SMAD3 (SMAD Family Member 3) were also replicated (Mbarek et al., 2016). We also ran the GWAS with a dominance model that identified a further locus ADRB2 on chr 5. These results have been contributed to the International Twinning Genetics Consortium for inclusion in the next GWAS meta-analysis (Mbarek et al., in press).

In both population-based and clinical cohorts, cross-sectional and longitudinal studies have reported associations between a range of non-specific markers of immune activation (e.g., pro-inflammatory cytokines) or chronic inflammation (e.g., C-reactive protein [CRP]) and depressive and other mood disorders (Dowlati et al. 2010; Hickie et al. 2018; Khandaker et al. 2017; Orsolini et al. 2022; Valkanova et al. 2013). The clinico-pathological significance, and directional relationships, of these associations tended to be downplayed as the systemic levels of these inflammatory markers were not in the ranges typical of active infective, inflammatory or significant autoimmune diseases.

Newcastle disease (ND) is a notifiable disease affecting chickens and other avian species caused by virulent strains of Avian paramyxovirus type 1 (APMV-1). While outbreaks of ND can have devastating consequences, avirulent strains of APMV-1 generally cause subclinical infections or mild disease. However, viruses can cause different levels of disease in different species and virulence can evolve following cross-species transmission events. This report describes the detection of three cases of avirulent APMV-1 infection in Great Britain (GB). Case 1 emerged from the ‘testing to exclude’ scheme in chickens in Shropshire while cases 2 and 3 were made directly from notifiable avian disease investigations in chicken broilers in Herefordshire and on premises in Wiltshire containing ducks and mixed species, respectively). Class II/genotype I.1.1 APMV-1 from case 1 shared 99.94% identity to the Queensland V4 strain of APMV-1. Class II/genotype II APMV-1 was detected from case 2 while the class II/genotype I.2 virus from case 3 aligned closely with strains isolated from Anseriformes. Exclusion of ND through rapid detection of avirulent APMV-1 is important where clinical signs caused by avirulent or virulent APMV-1s could be ambiguous. Understanding the diversity of APMV-1s circulating in GB is critical to understanding disease threat from these adaptable viruses.

When you think of 1960s anarchism, community playgrounds and financial planning for tenants’ associations may not spring to mind, yet these, along with similar topics, were Anarchy's (1961–1970) staple fare. The A5 monthly, edited by British journalist Colin Ward (1924–2010), maintained a steady output of ‘anarchist applications’ in the spheres of education, housing, and community development. Although published during the 1960s, the origins and ethos of the journal lay in the previous decade. Responding to this heightened Cold War “moment,” Ward developed an idiosyncratic radical pragmatism prioritizing the practice of popular democracy over the theory of it. In reconstructing Anarchy's intellectual formation, this article contributes to revisionist scholarship acknowledging a more experimental radical culture in 1950s Britain than is usually granted, one that prefigured aspects of the later counterculture but also differed from it in important respects.

The European Union's position on “one China” has stood since the establishment of diplomatic relations with the People's Republic of China (PRC) in 1975. As a union of distinct member states, the nature of the European Union's (EU) foreign policymaking complicates efforts to maintain coherent common positions. Its effective “one China policy” (and those of its member states) is no exception. In recent years, the edges of the bloc's long-standing policy have started to fray as the EU–PRC relationship has become more fraught and many member states have sought to deepen their effective, if “unofficial,” engagement with Taiwan. I explore these changes to the EU's effective “one China policy” by employing a subsystems framework, starting from the position that the EU has foreign policies (rather than a singular policy) created through three subsystems. Through the Normative Power Europe lens, I explore the extent to which the actors pulling at these “threads” at the edges of the EU's policy are motivated by normative concerns. I argue that the “fraying” of the EU's “one China policy” is not the result of a conscious decision by the EU as a collective normative actor but stems from shifting preferences within the national and supranational subsystems.

A growing percentage of international aid is distributed through local nongovernmental organizations (NGOs). Scholarship is divided on how that aid affects domestic politics. One side argues that aid to NGOs reinforces the status quo. As NGOs become dependent on external funding, they lose sight of their original goals. The other side contends that channeling funds to NGOs generates associational activity; producing political change by empowering previously marginalized groups. We test these competing hypotheses in Rondonia, Brazil, measuring the impact of internationally funded NGO activity on voting behavior. We find that the impact of aid varies with the institutional environment. At the state level, more votes for the conservative governor came from municipalities whose NGOs received project money. In contrast, the same municipalities registered a significant shift to leftist candidates at the presidential level. The findings have broad implications for the impact international aid has on political competition, political change, and democracy.

Increasing interest in three-dimensional nanostructures adds impetus to electron microscopy techniques capable of imaging at or below the nanoscale in three dimensions. We present a reconstruction algorithm that takes as input a focal series of four-dimensional scanning transmission electron microscopy (4D-STEM) data. We apply the approach to a lead iridate, Pb$_2$Ir$_2$O$_7$, and yttrium-stabilized zirconia, Y$_{0.095}$Zr$_{0.905}$O$_2$, heterostructure from data acquired with the specimen in a single plan-view orientation, with the epitaxial layers stacked along the beam direction. We demonstrate that Pb–Ir atomic columns are visible in the uppermost layers of the reconstructed volume. We compare this approach to the alternative techniques of depth sectioning using differential phase contrast scanning transmission electron microscopy (DPC-STEM) and multislice ptychographic reconstruction.

Background: Healthcare facilities have experienced many challenges during the COVID-19 pandemic, including limited personal protective equipment (PPE) supplies. Healthcare personnel (HCP) rely on PPE, vaccines, and other infection control measures to prevent SARS-CoV-2 infections. We describe PPE concerns reported by HCP who had close contact with COVID-19 patients in the workplace and tested positive for SARS-CoV-2. Method: The CDC collaborated with Emerging Infections Program (EIP) sites in 10 states to conduct surveillance for SARS-CoV-2 infections in HCP. EIP staff interviewed HCP with positive SARS-CoV-2 viral tests (ie, cases) to collect data on demographics, healthcare roles, exposures, PPE use, and concerns about their PPE use during COVID-19 patient care in the 14 days before the HCP’s SARS-CoV-2 positive test. PPE concerns were qualitatively coded as being related to supply (eg, low quality, shortages); use (eg, extended use, reuse, lack of fit test); or facility policy (eg, lack of guidance). We calculated and compared the percentages of cases reporting each concern type during the initial phase of the pandemic (April–May 2020), during the first US peak of daily COVID-19 cases (June–August 2020), and during the second US peak (September 2020–January 2021). We compared percentages using mid-P or Fisher exact tests (α = 0.05). Results: Among 1,998 HCP cases occurring during April 2020–January 2021 who had close contact with COVID-19 patients, 613 (30.7%) reported ≥1 PPE concern (Table 1). The percentage of cases reporting supply or use concerns was higher during the first peak period than the second peak period (supply concerns: 12.5% vs 7.5%; use concerns: 25.5% vs 18.2%; p Conclusions: Although lower percentages of HCP cases overall reported PPE concerns after the first US peak, our results highlight the importance of developing capacity to produce and distribute PPE during times of increased demand. The difference we observed among selected groups of cases may indicate that PPE access and use were more challenging for some, such as nonphysicians and nursing home HCP. These findings underscore the need to ensure that PPE is accessible and used correctly by HCP for whom use is recommended.

Funding: None

Disclosures: None

The 2016–17 European outbreak of H5N8 HPAIV (Clade 2.3.4.4b) affected a wider range of avian species than the previous H5N8 outbreak (2014–15), including an incursion of H5N8 HPAIV into gamebirds in England. Natural infection of captive-reared pheasants (Phasianus colchicus) led to variable disease presentation; clinical signs included ruffled feathers, reluctance to move, bright green faeces, and/or sudden mortality. Several birds exhibited neurological signs (nystagmus, torticollis, ataxia). Birds exhibiting even mild clinical signs maintained substantial levels of virus replication and shedding, with preferential shedding via the oropharyngeal route. Gross pathology was consistent with HPAIV, in gallinaceous species but diphtheroid plaques in oropharyngeal mucosa associated with necrotising stomatitis were novel but consistent findings. However, minimal or modest microscopic pathological lesions were detected despite the systemic dissemination of the virus. Serology results indicated differences in the timeframe of exposure for each case (n = 3). This supported epidemiological conclusions confirming that the movement of birds between sites and other standard husbandry practices with limited hygiene involved in pheasant rearing (including several fomite pathways) contributed to virus spread between premises.

Recent work has revived interest in the scattering matrix formulation of electron scattering in transmission electron microscopy as a stepping stone toward atomic-resolution structure determination in the presence of multiple scattering. We discuss ways of visualizing the scattering matrix that make its properties clear. Through a simulation-based case study incorporating shot noise, we shown how regularizing on this continuity enables the scattering matrix to be reconstructed from 4D scanning transmission electron microscopy (STEM) measurements from a single defocus value. Intriguingly, for crystalline samples, this process also yields the sample thickness to nanometer accuracy with no a priori knowledge about the sample structure. The reconstruction quality is gauged by using the reconstructed scattering matrix to simulate STEM images at defocus values different from that of the data from which it was reconstructed.

The federal Safe Drinking Water Act (SDWA), as amended in 1996, enables benefit-cost analysis (BCA) to be used in setting federal drinking water standards, known as MCLs. While BCAs are typically conceived of as a tool to inform efficiency considerations by helping to identify MCL options that maximize net social benefits, in this paper we also illustrate how important equity and affordability considerations can be brought to light by suitably applying BCAs to drinking water regulations, especially in the context of communities served by relatively small water systems. We examine the applicability and relevance of health-health analysis (HHA), and provide an empirical evaluation of the risk tradeoffs that may be associated with the MCL established for arsenic. We find that the cost-associated risks may offset a nontrivial portion of the cancer risk reduction benefits attributed to the MCL (e.g., the additional adverse health impacts from the costs may be roughly half as large as the number of cancer cases avoided). This reveals the relevance of using the HHA approach for examining net benefits of MCLs in small drinking water utilities, and raises issues related to whether and how these cost-associated health risks should be considered in BCAs for drinking water standards.

Scanning transmission electron microscopy (STEM) allows for imaging, diffraction, and spectroscopy of materials on length scales ranging from microns to atoms. By using a high-speed, direct electron detector, it is now possible to record a full two-dimensional (2D) image of the diffracted electron beam at each probe position, typically a 2D grid of probe positions. These 4D-STEM datasets are rich in information, including signatures of the local structure, orientation, deformation, electromagnetic fields, and other sample-dependent properties. However, extracting this information requires complex analysis pipelines that include data wrangling, calibration, analysis, and visualization, all while maintaining robustness against imaging distortions and artifacts. In this paper, we present py4DSTEM, an analysis toolkit for measuring material properties from 4D-STEM datasets, written in the Python language and released with an open-source license. We describe the algorithmic steps for dataset calibration and various 4D-STEM property measurements in detail and present results from several experimental datasets. We also implement a simple and universal file format appropriate for electron microscopy data in py4DSTEM, which uses the open-source HDF5 standard. We hope this tool will benefit the research community and help improve the standards for data and computational methods in electron microscopy, and we invite the community to contribute to this ongoing project.

The invention of silicon drift detectors has resulted in an unprecedented improvement in detection efficiency for energy-dispersive X-ray (EDX) spectroscopy in the scanning transmission electron microscope. The result is numerous beautiful atomic-scale maps, which provide insights into the internal structure of a variety of materials. However, the task still remains to understand exactly where the X-ray signal comes from and how accurately it can be quantified. Unfortunately, when crystals are aligned with a low-order zone axis parallel to the incident beam direction, as is necessary for atomic-resolution imaging, the electron beam channels. When the beam becomes localized in this way, the relationship between the concentration of a particular element and its spectroscopic X-ray signal is generally nonlinear. Here, we discuss the combined effect of both spatial integration and sample tilt for ameliorating the effects of channeling and improving the accuracy of EDX quantification. Both simulations and experimental results will be presented for a perovskite-based oxide interface. We examine how the scattering and spreading of the electron beam can lead to erroneous interpretation of interface compositions, and what approaches can be made to improve our understanding of the underlying atomic structure.