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Amis’s Holocaust novels make an ethical demand on the reader: to bear witness to their narrators’ failures to witness the atrocities they narrate even as they narrate them. The Zone of Interest dramatises an enabling banality that allows genocide to be conceptualised as a set of logistical problems, which the reader is expected to resist. But Amis here takes the banality of evil further, to the point of rendering the Nazi ideology that drove the genocide secondary to personal insecurities and petty grievances. Time’s Arrow, on the other hand, raises the question of banality only to reject it, presenting us with a perpetrator that embodies a ‘metaphysical’ evil. This is evil that is lifted out of the material world in which it is instantiated, and so the ideological causes of the Holocaust are again pushed to the sidelines. Both of Amis’s Holocaust novels, in short, risk depoliticising the Holocaust.
This chapter explores how Cyprus’ extreme-right National Popular Front’s (ELAM) visual environmental communication involves positioning itself as liberators of a sacred national territory by showcasing the masculine, self-described ELAMite as the saviour of the (female) enslaved and endangered land. Here, female is to male what nature is to culture. Against this background, this analysis illuminates how far-right representations of the environment reproduce relations of domination. More specifically, the chapter analyses 109 images addressing environmental themes in articles and press releases on ELAM’s website between 2016 and 2021. The findings point to the presence of three major themes: first, the barbed wire in occupied Cyprus; second, the protection of natural gas resources; and third, saving the land from fires. The analysis follows Barthes’ levels of meaning in visual inquiry (denotation, connotation, mythology) and argues that these images represent gendered codes of purity and control which are shared concepts both in nationalist ideologies and performances of hegemonic masculinities. That is, ELAM’s nostalgia and their belief in liberating the island from occupation is a gendered project that aims to restore not only the integrity of the national land but also a heroic version of the Greek Cypriot militarised masculinity.
A semi-automated surveillance system for surgical site infections (SSIs), SPICMI (Surveillance and Prevention Program for Infectious Risk in Surgery and Interventional Medicine), has been implemented in French hospitals, leveraging data from electronic health records (EHRs).
Objective:
To evaluate the performance of the SPICMI algorithm in detecting SSIs in orthopedic and digestive surgery.
Setting:
Surveillance data were collected annually from the EHRs. The algorithm identified suspected SSIs based on two criteria: (1) surgical revision during the index stay or readmission, (2) positive microbiological samples from the wound. Suspected SSIs identified were subsequently validated by surgeons.
Methods:
A stochastic modeling approach was used to estimate probability intervals for performance indicators. Various detection scenarios were constructed based on SPICMI criteria. Logistic regression analysis was performed using surveillance data. Data unavailable in the database were estimated through a literature review and expert opinions.
Results:
The probability of surgical revision following an SSI varied significantly between surgical specialties, ranging from 92% in orthopedic surgery to 45.2% in gynecology. In orthopedic and digestive surgery, the SPICMI algorithm demonstrated good reliability for detecting SSIs in minimizing false-negative and false-positive cases (Youden index: 0.96 and 0.79, respectively). Sensitivity (Se) was lower in digestive surgery (0.7–0.9) compared to orthopedic surgery (0.9–1), while specificity (Sp) remained high (0.9–1) in both specialties.
Conclusion:
The SPICMI algorithm shows potential to support efficient use of time and resources in SSIs surveillance management. Further evaluation is needed with a broader panel of surgery procedures.
This study describes the management and outcomes of temporal bone fractures resulting from falls.
Methods
We retrospectively reviewed patients with traumatic temporal bone fractures from 2018 through 2022.
Results
We analysed 171 patients with temporal bone fractures, 62 (36.3 per cent) of which occurred secondary to falls. Fall patients were significantly older than non-fall patients (mean age 46 vs. 38 years; p = 0.0079) and had higher Modified Frailty Index-5 scores (0.63 vs. 0.20; p = 0.0003). Fall patients had shorter hospital stays (10.1 vs. 15.8 days; p = 0.015), were more frequently discharged home (66.1 vs. 44.0 per cent; p = 0.007) and were less likely to experience non-resolving facial nerve weakness (6.5 vs. 21.1 per cent; p = 0.030).
Conclusion
Patients with temporal bone fractures from falls are older and frailer than non-fall patients and have unique preventative and rehabilitation needs.
Relationships between characters are not just themes in a story but key elements that shape how plots unfold. This article presents a large-scale study of relational arcs, the trajectories of ties, such as kinship, romance, alliance and enmity as they rise and fall across the course of a novel. We build on the Artificial Relationships in Fiction dataset, which contains over 120,000 automatically annotated relationships from 96 novels published between 1850 and 1950. Our study makes four contributions. First, we show that relationship dynamics can be modeled as arcs that highlight recurring narrative patterns, such as conflicts peaking near the climax or romances resolving toward the end. Second, we use temporal normalization to compare books of very different lengths, allowing us to identify consistent trends across the corpus. Third, we demonstrate that genres and historical periods leave clear relational “fingerprints.” For instance, domestic fiction emphasizes family ties, while adventure stories highlight shifting alliances and adversaries. Finally, we cluster arcs into four common shapes (Rise, U-shape, Decline and Oscillating) that echo well-known narrative prototypes. By bringing narratology together with modern natural language processing, we argue that relationships provide a measurable grammar of plot. This approach offers new resources for literary analysis, new methods for computational modeling of narrative, and fresh evidence about how cultural storytelling patterns change over time.
While much research has addressed the regressive anti-vax protests, this Element focuses on campaigns by progressive social movements to promote the development of vaccines for Covid-19 and ensure their equal access on a global level. Over the course of the pandemic, health and care have become central claims, mobilising health workers and patients as well as citizens in general. Together with various local and national social movement organizations which converged on health rights, through the use of care and cure as bridging frames, transnational campaigns addressing patents on vaccines also unfolded. This Element analyses these transnational campaigns, with particular attention to their organisational models, repertoires of action and collective framing. It assesses their outcomes by considering the complex sets of opportunities and constraints that the Covid-19 pandemic presented for progressive social movements that fight for access to medicines and cures at a global level.
Clozapine remains one of the most effective antipsychotic medications for treatment-resistant schizophrenia. However, its use is limited by significant metabolic and rare neurological side effects. The variability in patients’ susceptibility to these adverse effects suggests an unidentified genetic predisposition, which is critical to personalizing treatment.
Objectives
This review aims to systematically investigate the genetic variants involved in the development of metabolic and neurological side effects in patients treated with clozapine. Specifically, it seeks to elucidate the pathways participating in the occurrence of these adverse reactions and identify genetic markers for personalized therapeutic approaches.
Methods
A literature search was conducted across multiple databases for studies published in recent years. Data were extracted from cohort studies and case-control studies based on predefined criteria, using keywords such as “clozapine”, “metabolic side effects”, “neurological side effects”, “pharmacogenetics”.
Results
Preliminary results identified that variants in the FTO gene, known for its role in adipogenesis and energy homeostasis, were linked to enhanced adiposity and altered leptin signaling, contributing to the metabolic syndrome. Similarly, APOE gene was strongly correlated with increased risk of severe weight gain, dyslipidemia, and insulin resistance due to association with impaired lipid transport and metabolism.
In the context of neurological side effects, SNPs within the DRD2 Taq1A polymorphism, which affects dopamine receptor density and signaling, were associated with a higher incidence of extrapyramidal symptoms and tardive dyskinesia in patients on clozapine. The COMT Val158Met polymorphism, known to modulate prefrontal catecholamine degradation, was linked to cognitive impairments and clozapine-induced sedation.
Next-generation sequencing (NGS) enlightens rare SNPs, copy number variations (CNVs) and novel variants in genes related to drug metabolism, such as CYP1A2 and CYP2D6, allowing for the identification of complex genetic interactions. Furthermore, patients with high polygenic risk scores (PRS) exhibited a markedly increased likelihood of developing severe metabolic and neurological side effects, underscoring the utility of PRS in stratifying patient risk.
Conclusions
In summary, our findings demonstrate that genetic factors are key contributors to the development of clozapine-induced metabolic and neurological side effects. Variations in genes related to drug metabolism, neurotransmitter regulation, and metabolic pathways significantly influence individual susceptibility to these adverse effects. A deeper understanding of pharmacogenetic approaches could offer the potential for more personalized and precise treatment strategies, reducing adverse effects and improving drug tolerance.
Thyroid and sex hormones play pivotal roles in the regulation of various physiological processes, including brain function. Dysregulation of these hormones has been increasingly associated with a range of neuropsychiatric disorders, including depression, anxiety, cognitive impairment, and mood disorders.
Objectives
This review aims to systematically examine the correlation between thyroid and sex hormones disorders and the spectrum of emerging neuropsychiatric manifestations, enlightening the pathophysiological mechanisms.
Methods
A literature search was performed in many databases including PubMed, Web of Science, and Google Scholar for studies published in recent years. Eligible randomized controlled trials, observational studies, and systematic reviews examining neuropsychiatric outcomes in patients with thyroid or sex hormone disorders were included. Findings were synthesized both quantitatively, with meta-analyses where possible, and qualitatively, with thematic analysis for heterogeneous data.
Results
The review identified a strong association between thyroid dysfunctions and neuropsychiatric disorders such as depression, anxiety, and cognitive decline. Hypothyroidism was consistently linked with depressive symptoms likely due to impaired serotonergic and dopaminergic neurotransmission, along with decreased hippocampal neurogenesis. Conversely, hyperthyroidism, characterized by elevated thyroid hormone levels, was associated with heightened anxiety, irritability, and emotional lability, possibly through dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and increased sympathetic nervous system activity.
In the context of sex hormone disorders, estrogen deficiency during menopause was correlated with a significant increase in behavioral and cognitive impairments, potentially mediated by reduced modulation of serotonin receptors, diminished synaptic plasticity, and increased neuroinflammatory responses. Similarly, testosterone decline in aging men was linked to mood and cognitive disorders, with evidence pointing to disruptions in androgen receptor signaling and alterations in γ-aminobutyric acid (GABA)ergic and glutamatergic pathways.
Conclusions
This review underscores the significant link between thyroid dysfunctions, particularly hypothyroidism and hyperthyroidism and mood disorders such as depression and anxiety, while also indicates that estrogen deficiency and testosterone decline contribute to cognitive impairments and emotional disturbances. These findings help the healthcare providers to recognize neuropsychiatric symptoms as potential indicators of underlying endocrine disorders.
We propose a novel approach to check whether individual behaviour in binary-choice participation games is consistent with the restrictions imposed by symmetric models. This approach allows in particular an assessment of how much cluster-heterogeneity a symmetric model can tolerate to remain consistent with its behavioural restrictions. We assess our approach with data from market-entry experiments which we analyse through the lens of ‘Exploration versus Exploration’ (EvE, which is equivalent to Logit-QRE) or of Impulse Balance Equilibrium (IBE). We find that when the symmetry assumption is imposed, both models are typically rejected when assuming pooled data and IBE yields more data-consistent estimates than EvE, i.e., IBE’s estimates of session and pooled data are more consistent than those of EvE. When relaxing symmetry, EvE (IBE) is rejected for 17% (42%) of the time. Although both models support cluster-heterogeneity, IBE is much less likely to yield over-parametrised specifications and insignificant estimates so it outperforms EvE in accommodating a model-consistent cluster-heterogeneity. The use of regularisation procedures in the estimations partially addresses EvE’s shortcomings but leaves our overall conclusions unchanged.
U.S. adaptive optics telescopes using laser guide stars for an artificial reference source are impacted by the presence of satellite constellations (SATCONs) because of the requirement to follow Department of Defense laser deconfliction protocol as administered by the U.S. Space Command’s Laser Clearinghouse. The Laser Deconfliction protocol is designed to protect damage to satellites and their operation due to inadvertent illumination. As SATCONs begin to dominate the number of satellites in orbit they contribute highly to the number of closure windows when the astronomical lasers cannot be propagated. If left unchecked, the proposed number of SATCONs over the next decade will severely impact the laser open-shutter time, especially for the U.S. extremely large telescopes (US-ELTs) reducing the competitiveness of U.S. astronomical adaptive optics. Mitigation of the closure windows is therefore important.
Nowadays public policymakers are offered with opportunities to take data-driven evidence-based decisions by analyzing the very large volumes of policy-related data that are generated through different channels (e.g., e-services, mobile apps, social media). Machine learning (ML) and artificial intelligence (AI) tehcnologies ease and automate the analysis of large policy-related datasets, which helps policymakers to realize a shift toward data-driven decisions. Nevertheless, the deployment and use of AI tools for public policy development is also associated with significant technical, political, and operation challenges. For instance, AI-based policy development solutions must be transparent and explainable to policymakers, while at the same time adhering to the mandates of emerging regulations such as the AI Act of the European Union. This paper introduces some of the main technical, operational, regulatory compliance challenges of AI-based policymaking. Accordingly, it introduces technological solutions for overcoming them, including: (i) a reference architecture for AI-based policy development, (ii) a virtualized cloud-based tool for the specification and implementation of ML-based data-driven policies, (iii) a ML framework that enables the development of transparent and explainable ML models for policymaking, and (iv) a set of guidelines for using the introduced technical solutions to achieve regulatory compliance. The paper ends up illustrating the validation and use of the introduced solutions in real-life public policymaking cases for various local governments.
The asteroid belt is a unique source of information on some of the most important questions facing solar system science. These questions include the sizes, numbers, types and orbital distributions of the planetesimals that formed the planets, and the identification of those asteroids that are the sources of meteorites and near-Earth asteroids. Answering these questions requires an understanding of the dynamical evolution of the asteroid belt, but this evolution is governed by a complex interplay of mechanisms that include catastrophic disruption, orbital evolution driven by Yarkovsky radiation forces, and chaotic orbital evolution driven by gravitational forces. While the timescales of these loss mechanisms have been calculated using estimates of some critical parameters that include the thermal properties, strengths and mean densities of the asteroids, we argue here that the uncertainties in these parameters are so large that deconvolution of the structure of the asteroid belt must be guided primarily by observational constraints. We argue that observations of the inner asteroid belt indicate that the size-frequency distribution is not close to the equilibrium distribution postulated by Dohnanyi (1969). We also discuss the correlations observed between the sizes and the orbital elements of the asteroids. While some of these correlations are significant and informative, others are spurious and may arise from the limitations of the Hierarchical Clustering Method that is currently used to define family membership.
The figure of the spy is almost invariably tied to the concept of the nation and of the sovereign state – so much so that, as this chapter suggests, the removal of the state from the spy story would amount to what might be thought of as an ontological reconfiguration of the genre. William Gibson’s Blue Ant trilogy – Pattern Recognition (2003), Spook Country (2007), and Zero History (2010) – effects just such a reconfiguration. The chapter traces the ways in which Gibson reimagines the figure of the spy in the age of the global and unearths the implications of this transformation. While the centrality of the nation-state has much to do with the conservativism that typically underpins spy fiction, the absence of the state in the Blue Ant trilogy’s global setting does not serve to transform a fundamentally conservative genre into a progressive one; rather, it points to something that is in fact more regressive: the emergence of a neo-feudal world.
In 2014, the FDA approved Innovative Health Solutions’ wearable NSS-2 Bridge device for chronic and acute pain management. In 2017, the FDA cleared the device’s use for managing opioid withdrawal symptoms. Critics have raised substantive concerns about the evidence used to support the determination that the device could safely and effectively be used for opioid withdrawal, and the methods used by the manufacturer (both pre- and post-FDA approval) to gain support for the implementation of the device. The manufacturer and pharmaceutical companies have begun to engage with judges and other key personnel associated with drug courts and other court systems around the country with significant censuses of cases involving people who use opioids. This chapter draws upon empirical and theoretical research approaches to address significant ethical, public health, and oversight concerns raised by these burgeoning relationships, including the following questions: (1) How prevalent is industry-court personnel contact? (2) What do court personnel receive from industry? (3) How might such contacts affect the lives of justice-involved people who use opioids? (4) What ethical and health-related concerns arise with the development of such relationships? (5) What, if any, oversight do (or could) local and state court systems provide for industry-court personnel relationships?
The comprehension of Spanish verbal future and past tense of children with developmental language disorder (DLD) was evaluated in an eye-tracking experiment with 96 Spanish- and Catalan-speaking participants distributed in 4 groups: 24 children with DLD (Mage 7.8 years), 24 children with the same chronological age (Mage 7.8), 24 children with the same linguistic level (Mage 6.8 years), and 24 adults (Mage 22.5 years). Empirical data revealed that children with DLD can comprehend verbal tense, at least in the present experimental conditions. Based on the empirical results and despite some minor differences between the DLD group and the chronological control group, we suggest that tense morphology comprehension in DLD might be more typical than what is generally considered. Additionally, we propose that verbal comprehension difficulties in children with DLD might be less related to the lack of understanding of specific morphological markers, and more to an accumulation of difficulty which leads to a linguistic processing slowdown.
Studies on the processing of non-active (NACT) voice have indicated that passive sentences are more difficult to comprehend and require more time to process. Children with Reading Difficulties (RDs) face problems with sentence comprehension, which are often attributed to phonological processing, working memory, syntactic awareness limitations, or a maturation delay. Using an online self-paced reading task, we investigated the effect of voice morphology and argument structure on sentence processing in 3 groups of participants; 30 children RDs, 28 Age-Matched (AM) controls without RDs, and 28 young Beginning Readers (BRs). Our results suggest that although the RDs and BR groups present similar reading times, their reading patterns differ qualitatively. Beginning Readers experienced greater processing delays when processing NACT structures, suggesting that they have not yet fully grasped the properties of the various NACT verbs. However, the RDs group presents effects not found in the BR group; children with RDs were sensitive to the properties of the different types of NACT verbs showing (a) evidence that the language processor successfully engages in predictions based on the morphosyntactic and lexical characteristics of verbs and (b) preference for default/prototypical readings. These results point toward processing limitations that are greatly affected by syntactic complexity.
Impaired response to stress and a pathological activation of the hypothalamic-pituitary-adrenal axis have been implicated in the pathophysiology of schizophrenia
Objectives
To measure serum ACTH, cortisol and DEHA-S levels in drug-naïve, first-episode patients with psychosis.
Methods
Results are reported as mean (standard deviation, range). Paired t-test or Wilcoxon signed rank test were performed for group comparisons. The level of significance was set at p-value<0.05. Statistical analysis was performed with Stata 15.1.
Results
Data were included for 110 subjects (70 men, 40 women); 55 patients and 55 controls matched for age and sex. Mean age was 31.3 years (8.7, 18-48) in patients and 31.4 years (8.9, 17-49) in controls. Serum cortisol and Cortisol/DHEA-S ratio were statistically significantly lower in patients [12.6μg/dl (4.5, 3.5-24.5) and 5.3 (3.6, 1.3-19.5), respectively] compared to controls [15.5 μg/dl (4.9, 4.2-30.1) and 8 (4.7, 1.1-25.5), respectively] (p-value=0.0068 and 0.0005, respectively). Additionally, serum DHEA-S was statistically significantly higher in patients [306.5 μg/dl(165.4, 70-790)] compared to controls [240.1 μg/dl(113.5, 46-597)] (p-value=0.0114). ACTH was also higher in patients [28.5 pg/ml(15.7, 6.2-73.9)] than controls [26.5 pg/ml (15.3, 7-70.5)] but this difference wasn’t statistically significant (p-value=0.6359).
Conclusions
We report elevated DEHA-S, decreased cortisol levels and decreased cortisol/DEHA-S ratio in the patients’ compared to the controls’ group.
We have shown that in the inner belt the loss of asteroids from the ν6 secular resonance and the 3:1 Jovian mean motion resonance accounts for the observation that the mean size of the asteroids increases with increasing orbital inclination. We have used that observation to constrain the Yarkovsky loss timescale and to show that the family asteroids are embedded in a background population of old ghost families. We argue that all the asteroids in the inner belt originated from a small number of asteroids and that the initial mass of the belt was similar to that of the present belt. We also show that the observed size frequency distribution of the Vesta asteroid family was determined by the action of Yarkovsky forces, and that the age of this family is comparable to the age of the solar system.
OBJECTIVES/SPECIFIC AIMS: This study seeks to understand the relationship between opioid prescribing and patient satisfaction among non-surgical, hospitalized patients. As part of this study, we qualitatively examined challenges in delivering safe and patient-centered care through voices of physicians’, and nurses.’ METHODS/STUDY POPULATION: We collected data through in-person interviews using semi-structured guides tailored to the informant roles. Study participants came from 1 healthcare system located in a mid-Western state. Each interview lasted 30–45 minutes, was audio-recorded with consent, and transcribed for analysis. Two researchers each coded 17 transcripts for discussions around patient-centeredness (including patient satisfaction, patient experiences), and patient safety for hospitalized patients experiencing pain. Analysis followed a general inductive approach, where researchers identified themes related to the research questions using an open coding technique. They discussed and reached consensus on all codes, and extracted several preliminary themes. The analysis was supported by NVivo software. RESULTS/ANTICIPATED RESULTS: The following themes emerged: (1) complex decision-making process to prescribe opioids for hospitalized patients; (2) the role of objective findings in prescribing decisions; (3) bargaining process in prescribing opioids; (4) balancing patient-centeredness and patient safety for selected populations; (5) opioids are the predominant medications for pain care. DISCUSSION/SIGNIFICANCE OF IMPACT: Clinicians’ decision to prescribe opioids for nonsurgical hospitalized patients is based on multiple factors, including patient’s condition, patient’s preference for pain medications, or standard hospital’s pain care regimen. Interventions that improve clinicians’ ability to prescribe opioids may be needed to improve delivery of patient-centered and safe pain care.
The observed size-frequency distributions (SFDs) of the five major asteroid families in the Inner Main Belt (IMB), defined by Nesvorný (2015) using the Hierarchical Clustering Method (Zappala et al. 1990), are distinctly different and deviate significantly from the linear log-log relation described by Dohnanyi (1969). The existence of these differences in the SFDs, and the fact that the precursor bodies of the major families have distinctly different eccentricities and inclinations, provides an explanation for the observations that the mean sizes of both the family and the non-family asteroids are correlated with their mean proper eccentricities and anti-correlated with their mean proper inclinations. We deduce from this, and from the fact that the SFDs of the family and the non-family asteroids are almost identical, that the family and most of the non-family asteroids in the IMB have a common origin (Dermott et al. 2018).