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Background Increased rates of visual impairment are observed in people with schizophrenia. Aims We assessed whether genetically predicted poor distance acuity is causally associated with schizophrenia, and whether genetically predicted schizophrenia is causally associated with poorer visual acuity. Method We used bidirectional, two-sample Mendelian randomisation to assess the effect of poor distance acuity on schizophrenia risk, poorer visual acuity on schizophrenia risk and schizophrenia on visual acuity, in European and East Asian ancestry samples ranging from approximately 14 000 to 500 000 participants. Genetic instrumental variables were obtained from the largest available summary statistics: for schizophrenia, from the Psychiatric Genomics Consortium; for visual acuity, from the UK Biobank; and for poor distance acuity, from a meta-analysis of case–control samples. We used the inverse variance-weighted method and sensitivity analyses to test validity of results. Results We found little evidence that poor distance acuity was causally associated with schizophrenia (odds ratio 1.00, 95% CI 0.91–1.10). Genetically predicted schizophrenia was associated with poorer visual acuity (mean difference in logMAR score: 0.024, 95% CI 0.014–0.033) in European ancestry samples, with a similar but less precise effect that in smaller East Asian ancestry samples (mean difference: 0.186, 95% CI –0.008 to 0.379). Conclusions Genetic evidence supports schizophrenia being a causal risk factor for poorer visual acuity, but not the converse. This highlights the importance of visual care for people with psychosis and refutes previous hypotheses that visual impairment is a potential target for prevention of schizophrenia.

BackgroundGenetic Risk Scores (GRS) for predicting dementia risk have mostly been used in people of European ancestry with limited testing in other ancestry groups.MethodsWe conducted a logistic regression with all-cause dementia as the outcome and z-standardised GRS as the exposure across diverse ethnic groups.FindingsThere was variation in frequency of APOE alleles across ethnic groups. Per standard deviation (SD) increase in z-GRS including APOE, the odds ratio (OR) for dementia was 1.73 (95%CI 1.69-1.77). Z-GRS excluding APOE also increased dementia risk (OR 1.21 per SD increase, 95% CI 1.18-1.24) and there was no evidence that ethnicity modified this association. Prediction of secondary outcomes was less robust in those not of European ancestry when APOE was excluded from the GRS.Interpretationz-GRS derived from studies in people of European ancestry can be used to quantify genetic risk in people from more diverse ancestry groups. Urgent work is needed to include people from diverse ancestries in future genetic risk studies to make this field more inclusive.

We performed a systematic analysis of blood DNA methylation profiles from 4483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia, and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.

Abstract Artificial intelligence (AI) and machine learning (ML) pose a challenge for achieving science that is both reproducible and replicable. The challenge is compounded in supervised models that depend on manually labeled training data, as they introduce additional decision‐making and processes that require thorough documentation and reporting. We address these limitations by providing an approach to hand labeling training data for supervised ML that integrates quantitative content analysis (QCA)—a method from social science research. The QCA approach provides a rigorous and well‐documented hand labeling procedure to improve the replicability and reproducibility of supervised ML applications in Earth systems science (ESS), as well as the ability to evaluate them. Specifically, the approach requires (a) the articulation and documentation of the exact decision‐making process used for assigning hand labels in a “codebook” and (b) an empirical evaluation of the reliability” of the hand labelers. In this paper, we outline the contributions of QCA to the field, along with an overview of the general approach. We then provide a case study to further demonstrate how this framework has and can be applied when developing supervised ML models for applications in ESS. With this approach, we provide an actionable path forward for addressing ethical considerations and goals outlined by recent AGU work on ML ethics in ESS.

System requirements specify how a system meets stakeholder needs. They are a partial definition of the system under design in natural language that may be restricted in syntax terms. Any natural language specification inevitably lacks a unique interpretation and includes underspecified terms and inconsistencies. If the requirements are not validated early in the system development cycle and refined, as needed, specification flaws may cause costly cycles of corrections in design, implementation and testing. However, validation should be based on a consistent interpretation with respect to a rigorously defined semantic context of the domain of the system. We propose a specification approach that, while sufficiently expressive, it restricts the requirements definition to terms from an ontology with precisely defined concepts and semantic relationships in the domain of the system under design. This enables a series of semantic analyses, which guide the engineer towards improving the requirement specification as well as eliciting tacit knowledge. The problems addressed are prerequisites to enable the derivation of verifiable specifications, which is of fundamental importance for the design of critical embedded systems. We present the results from a case study of modest size from the space system domain, as well as an evaluation of our approach from the user’s point of view. The requirement types that have been covered demonstrate the applicability of the approach in an industrial context, although the effectiveness of the analysis depends on pre-existing domain ontologies.

The industry related to electric vehicles (EVs) has seen a substantial increase in recent years, as such vehicles have the ability to significantly reduce total CO2 emissions and the related global warming effect. In this paper, we focus on the problem of allocating EVs to charging stations, scheduling and pricing their charging. Specifically, we developed a Mixed Integer Program (MIP) which executes offline and optimally allocates EVs to charging stations. On top, we propose two alternative mechanisms to price the electricity the EVs charge. The first mechanism is a typical fixed-price one, while the second is a variation of the Vickrey–Clark–Groves (VCG) mechanism. We also developed online solutions that incrementally call the MIP-based algorithm and solve it for branches of EVs. In all cases, the EVs’ aim is to minimize the price to pay and the impact on their driving schedule, acting as self-interested agents. We conducted a thorough empirical evaluation of our mechanisms and we observed that they had satisfactory scalability. Additionally, the VCG mechanism achieved an up to 2.2% improvement in terms of the number of vehicles that were charged compared to the fixed-price one and, in cases where the stations were congested, it calculated higher prices for the EVs and provided a higher profit for the stations, but lower utility to the EVs. However, in a theoretical evaluation, we proved that the variant of the VCG mechanism being proposed in this paper still guaranteed truthful reporting of the EVs’ preferences. In contrast, the fixed-price one was found to be vulnerable to agents’ strategic behavior as non-truthful EVs can charge instead of truthful ones. Finally, we observed the online algorithms to be, on average, at 95.6% of the offline ones in terms of the average number of serviced EVs.

The processes involved in requirements engineering are some of the most, if not the most, important steps in systems development. The need for well-defined requirements remains a critical issue for the development of any system. Describing the structure and behavior of a system could be proven vague, leading to uncertainties, restrictions, or improper functioning of the system that would be hard to fix later. In this context, this article proposes SENSE, a framework based on standardized expressions of natural language with well-defined semantics, called boilerplates, that support a flow-down procedure for requirement management. This framework integrates sets of boilerplates and proposes the most appropriate of them, depending, among other considerations, on the type of requirement and the developing system, while providing validity and completeness verification checks using the minimum consistent set of formalities and languages. SENSE is a consistent and easily understood framework that allows engineers to use formal languages and semantics rather than the traditional natural languages and machine learning techniques, optimizing the requirement development. The main aim of SENSE is to provide a complete process of the production and standardization of the requirements by using semantics, ontologies, and appropriate NLP techniques. Furthermore, SENSE performs the necessary verifications by using SPARQL (SPIN) queries to support requirement management.