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“Looking into the future” well depicts one of the most significant concepts in cognitive neuroscience: the brain is constantly predicting future events. Such directedness toward the future has been recognized to be relevant to and beneficial for many aspects of information processing in humans, such as perception, motor and cognitive control, decision-making, theory of mind, and other cognitive processes. Because one of the most adaptive characteristics of the brain is to correct errors, the ability to look into the future represents the best chance to avoid repeating errors. Within the structures that constitute the “predictive brain,” the cerebellum has been proposed to have a central function, based on its ability to generate internal models. We suggested that “sequence detection” is the operational mode of the cerebellum in predictive processing. According to this hypothesis, the cerebellum detects and simulates repetitive patterns of temporally or spatially structured events and generates internal models that can be used to make predictions. Consequently, we demonstrate that the cerebellum recognizes serial events as a sequence, detects a sequence violation, and successfully reconstructs the correct sequence of events. Thus, we hypothesize that pattern detection and prediction and processing of anticipation are cerebellum-specific functions within the brain and that the sequence detection hypothesis links the multifarious impairments that are reported in patients with cerebellar damage. We propose that this cerebellar operational mode can advance our understanding of the pathophysiological mechanisms in various clinical conditions, such as schizophrenia and autism.

When the constitution of the Republic of Genoa was rewritten in 1528, the traditional distinction between nobili and popolari was abolished and the now unified ruling class was organised into 28 groups called alberghi, which were granted equal political representation by an elaborate and bizarre voting mechanism. Using data on the composition of the Genoese nobility in 1528, we simulate the rounds of voting, nominations, and sortition of the electoral protocol to reveal how they determined the allocation of power. Our analysis shows that the constitutional reform could not succeed in bringing concord to the nobility, as the system was heavily biased towards the popolari (later renamed nobili nuovi), who could gain control over all key magistracies. We also show that the use of the alberghi for office allocation made the system less favourable to the nobili nuovi, but only marginally so. These results help explain the persistence of political instability in Genoa after the 1528 reform, and they shed light on the voting system reforms that followed.

Vulvovaginal candidiasis (VVC) is a common infection, and high-quality studies report that misdiagnosis is frequent, with diagnostic testing needed to distinguish it from other causes of vaginitis and avoid inappropriate empiric treatment. However, few recent studies have evaluated U.S. healthcare providers’ testing practices for VVC in detail. We evaluated healthcare providers’ self-reported testing practices for VVC and treatment outcomes as part of a nationwide online survey in order to identify potential opportunities for improving VVC testing and treatment in the United States. Among 1,503 providers surveyed, 21.3% reported “always” (7.4%) or “usually” (13.9%) ordering diagnostic testing for patients with suspected VVC; this proportion was higher among gynecologists (36.0%) compared with family practitioners (17.8%) and internists (15.8%). Most providers (91.2%) reported that patients’ VVC “always” (6.4%) or “usually” (84.9%) responds to initial treatment. Whether the symptom resolution reported in this survey was truly related to VVC is unclear given high rates of misdiagnosis and known widespread empiric prescribing. With only about one-in-five providers reporting usually or always performing diagnostic testing for VVC despite guidelines recommending universal use, research is needed to address barriers to proper testing.

Despite preventive efforts, influenza epidemics are responsible for substantial morbidity and mortality every year in the United States (US). Vaccination strategies to reduce disease burden have been implemented. However, no previous studies have systematically estimated the annual economic burden of influenza epidemics, an estimate necessary to guide policy makers effectively. We estimate age- and risk-specific disease burden, and medical and indirect costs attributable to annual influenza epidemics in the United States. Using a probabilistic model and publicly available epidemiological data we estimated the number of influenza-attributable cases leading to outpatient visits, hospitalization, and mortality, as well as time lost from work absenteeism or premature death. With data from health insurance claims and projections of either earnings or statistical life values, we then estimated healthcare resource utilization associated with influenza cases as were their medical and productivity (indirect) costs in $2003. Based on 2003 US population, we estimated that annual influenza epidemics resulted in an average of 610,660 life-years lost (undiscounted), 3.1 million hospitalized days, and 31.4 million outpatient visits. Direct medical costs averaged $10.4 billion (95% confidence interval [C.I.], $4.1, $22.2) annually. Projected lost earnings due to illness and loss of life amounted to $16.3 billion (C.I., $8.7, $31.0) annually. The total economic burden of annual influenza epidemics using projected statistical life values amounted to $87.1 billion (C.I., $47.2, $149.5). These results highlight the enormous annual burden of influenza in the US. While hospitalization costs are important contributors, lost productivity from missed work days and lost lives comprise the bulk of the economic burden of influenza.

Optimal control mechanisms require prediction capabilities. If one cannot predict the consequences of a motor act or behaviour, one will continually collide with walls or become a social pariah. “Looking into the future” is thus one of the most important prerequisites for smooth movements and social interactions. To achieve this goal, the brain must constantly predict future events. This principle applies to all domains of information processing, including motor and cognitive control, as well as the development of decision-making skills, theory of mind, and virtually all cognitive processes. Sequencing is suggested to support the predictive capacity of the brain. To recognize that events are related, the brain must discover links among them in the spatiotemporal domain. To achieve this, the brain must often hold one event in working memory and compare it to a second one, and the characteristics of the two must be compared and correctly placed in space and time. Among the different brain structures involved in sequencing, the cerebellum has been proposed to have a central function. We have suggested that the operational mode of the cerebellum is based on “sequence detection” and that this process is crucial for prediction. Patterns of temporally or spatially structured events are conveyed to the cerebellum via the pontine nuclei and compared with actual ones conveyed through the climbing fibres olivary inputs. Through this interaction, data on previously encountered sequences can be obtained and used to generate internal models from which predictions can be made. This mechanism would allow the cerebellum not only to recognize sequences but also to detect sequence violations. Cerebellar pattern detection and prediction would thus be a means to allow feedforward control based on anticipation. We will argue that cerebellar sequencing allows implementation of prediction by setting the correct excitatory levels in defined brain areas to implement the adaptive response for a given pattern of stimuli that embeds sufficient information to be recognized as a previously encountered template. Here, we will discuss results from human and animal studies and correlate them with the present understanding of cerebellar function in cognition and behaviour.

Huanglonbing (HLB) is the most serious disease of citrus in the world, associated with three non-cultivable phloem-restricted bacteria Liberibacter asiaticus ( Las), L. africanus ( Laf) and L. americanus ( Lam). Las is transmitted by the Asian citrus psyllid , and has spread to several countries. The African psyllid , the vector of Laf occurs in Africa and neighbouring islands. Only two major citrus-growing regions - Australia/New Zealand and the Mediterranean Basin - are still HLB-free in the world. However, has recently been introduced into continental Europe (Portugal and Spain) and has become a potential threat to citrus production. The transmission of Las by had been postulated but never tested. To evaluate the risk of transmitting Las, comparative transmissions of Las by and were assessed. Transmission tests were performed on excised leaves and seedlings of with different inoculation access periods (in series) for both insect species. Quantifications of bacterial titers were made in excised leaves, seedlings three and six months after inoculation and on individual insects. Our results showed that was able to efficiently acquire Las. Furthermore, carried significantly higher bacterial titers than , and was able to efficiently transmit the bacteria to seedlings at a similar rate that highlighting the high risk of spread of the most aggressive variant of HLB ( Las) by in Europe. Thus, extreme precautions to prevent any entry of Las into Europe should be adopted.

We study a family of voting rules inspired by the peculiar protocol used for over 500 years by the Republic of Venice to elect its Doge. Lot-based indirect elections have two main features: a pool of delegates is chosen by lot out of a general assembly, and then they vote in a single winner election with qualified majority. Under the assumption that the assembly is divided into two factions, we characterise the win probability of the minority and show that these features promote a more equitable allocation of political representation, striking a balance between protecting the minority and giving proper recognition to the majority. We then consider this family of voting procedures from a constitutional perspective: we analyse how the electoral result varies with the college size and the winning threshold in order to understand how these two parameters can be tuned when drawing up electoral law. We find that minorities are better off with larger majority thresholds. The role of the college size, on the other hand, is ambiguous: a smaller college size offers more protection to sparse minorities; for more sizeable ones, it depends instead on the qualified majority required for the election.

What is already known about this topic? Risk for severe COVID-19 increases with age, disability, and underlying medical conditions. The SARS-CoV-2 Omicron variant is more infectious but has been associated with less severe disease. What is added by this report? In-hospital mortality among patients hospitalized primarily for COVID-19 decreased from 15.1% (Delta period) to 4.9% (later Omicron period; April–June 2022), despite high-risk patient groups representing a larger proportion of hospitalizations. During the later Omicron period, the majority of in-hospital deaths occurred among adults aged ≥65 years (81.9%) and persons with three or more underlying medical conditions (73.4%). What are the implications for public health practice? Vaccination, early treatment, and appropriate nonpharmaceutical interventions remain important public health priorities to prevent COVID-19 deaths, especially among persons most at risk.

The physicochemical properties of plant fibres are determined by the fibre morphology and structural features of the cell wall, which is composed of three main layers that differ in chemical composition and architecture. This composition and hierarchical structure are responsible for many of the mechanical properties that are desirable for industrial applications. As interactions between the lignocellulosic polymers at the molecular level are the main factor governing the final cohesion and mechanical properties of plant fibres, atomic force microscopy (AFM) is well suited for the observation and measurement of their physical properties at nanoscale levels. Given the complexity of plant cell walls, we have developed a strategy based on lignocellulosic assemblies with increasing complexity to understand the influence of the different polymers on the nanomechanical properties. Measurements of the indentation moduli performed on one type of lignified cell wall compared with those performed on the corresponding lignocellulosic films clearly show the importance of the lignin in the mechanical properties of cell walls. Through this strategy, we envision a wide application of bioinspired systems in future studies of the physical properties of fibres.

Background:Systemic diseases most frequently associated with uveitis are spondyloarthritis (SpA). Differences in the presentation of uveitis have been described in each type of SpA, however, this information is contradictory and scarce in the literature. The differentiation of these associated inflammatory processes has important therapeutic and prognostic implications and may condition the treatment of the underlying disease in Ophthalmology/Rheumatology Ocular Inflammation Interdisciplinary Units.Objectives:The aim of the study is to analyze the characteristics of non-infectious ocular inflammation in the different types of spondyloarthritis in a multidisciplinary ocular inflammation practice.Methods:Descriptive observational study including data from patients with a non-infectious inflammatory ocular process secondary to SpA evaluated in a multidisciplinary ocular inflammation consultation from January 2012 to January 2024. Demographic, ocular involvement, sequelae, and therapy data are comparatively analyzed. Quantitative variables were described as median and interquartile range (IQR) or mean and standard deviation (SD), and frequencies were used for the qualitative variables. Comparative analysis was performed using the IBM SPSS 21.0 program and the comparison of proportions using the chi-square test. P-values <0.05 were considered statistically significant.Results:From our “Inflammatory ocular process Registry” at La Paz University Hospital with a total of 564 patients included, we collected data from 147 patients with SpA (26%). Table 1 shows clinical characteristics in the global sample and in the different types of spondyloarthritis. In the comparative analysis, according to the type of spondyloarthritis, significant differences were found in the percentage of positive HLAB27 (p<0.01); being more frequent in ankylosing spondylitis (AS) and axial spondyloarthritis (AxSpA) than in the rest of the groups. The age of onset was significantly higher in AS and psoriatic arthritis (PsA) than in others (p<0.01). Regarding the ocular involvement, significant differences were found (p<0.01) in the pattern and course. Recurrent acute anterior uveitis (RAAU) pattern and the recurrent acute course were predominant in AS, axSpA and PsA. Bilateral acute anterior uveitis (BAAU) pattern and chronic forms were more frequent in peripheral spondyloarthritis (pSpA) and inflammatory bowel disease associated with spondyloarthritis (IbdSpA). Concerning the ophthalmological examination, significant differences (p<0.05) were found in the presence of keratic precipitates (more frequent in AS, axSpA and PsA), vitritis (higher proportion in PsA) and cataract (more frequent in AS, IbdSpA and PsA). No differences were found in sex, location/laterality of the uveitis (anterior and unilateral involvement are predominant in all cases), neither in complications such as visual impairment, synechiae, cystic macular edema, glaucoma, retinal vasculitis, epiretinian membrane or papilitis. Regarding therapy, there were significant differences (p<0.05) in the use of systemic corticosteroids; most commonly used in pSpA and PsA. The use of disease-modifying anti-rheumatic drugs (DMARDs) was also more frequent in pSpA and PsA without reaching statistical significance (p=0.056). There were no significant differences in the use of biological therapy.Conclusion:This study reveals differences in the inflammatory ocular involvement regarding the type of spondyloarthritis. Bilateral and chronic forms of uveitis were more frequently observed in IbdSpA o pSpA. Additionally, the use of systemic steroids and DMARDs was most common in pSpA and PsA.Table 1.REFERENCES:NIL.Acknowledgements:To the Ophthalmology/Rheumatology Ocular Inflammation Interdisciplinary Unit of La Paz University Hospital.Disclosure of Interests:None declared.