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Billions of nocturnally migrating birds move through increasingly photopolluted skies, relying on cues for navigation and orientation that artificial light at night (ALAN) can impair. However, no studies have quantified avian responses to powerful ground-based light sources in urban areas. We studied effects of ALAN on migrating birds by monitoring the beams of the National September 11 Memorial & Museum’s “Tribute in Light” in New York, quantifying behavioral responses with radar and acoustic sensors and modeling disorientation and attraction with simulations. This single light source induced significant behavioral alterations in birds, even in good visibility conditions, in this heavily photopolluted environment, and to altitudes up to 4 km. We estimate that the installation influenced ≈1.1 million birds during our study period of 7 d over 7 y. When the installation was illuminated, birds aggregated in high densities, decreased flight speeds, followed circular flight paths, and vocalized frequently. Simulations revealed a high probability of disorientation and subsequent attraction for nearby birds, and bird densities near the installation exceeded magnitudes 20 times greater than surrounding baseline densities during each year’s observations. However, behavioral disruptions disappeared when lights were extinguished, suggesting that selective removal of light during nights with substantial bird migration is a viable strategy for minimizing potentially fatal interactions among ALAN, structures, and birds. Our results also highlight the value of additional studies describing behavioral patterns of nocturnally migrating birds in powerful lights in urban areas as well as conservation implications for such lighting installations.

Orientation is a fundamental mental function that processes the relations between the behaving self to space (places), time (events), and person (people). Behavioral and neuroimaging studies have hinted at interrelations between processing of these three domains. To unravel the neurocognitive basis of orientation, we used highresolution 7T functional MRI as 16 subjects compared their subjective distance to different places, events, or people. Analysis at the individual-subject level revealed cortical activation related to orientation in space, time, and person in a precisely localized set of structures in the precuneus, inferior parietal, and medial frontal cortex. Comparison of orientation domains revealed a consistent order of cortical activity inside the precuneus and inferior parietal lobes, with space orientation activating posterior regions, followed anteriorly by person and then time. Core regions at the precuneus and inferior parietal lobe were activated for multiple orientation domains, suggesting also common processing for orientation across domains. The medial prefrontal cortex showed a posterior activation for time and anterior for person. Finally, the default-mode network, identified in a separate resting-state scan, was active for all orientation domains and overlapped mostly with person-orientation regions. These findings suggest that mental orientation in space, time, and person is managed by a specific brain system with a highly ordered internal organization, closely related to the default-mode network.

Delirium is a clinical syndrome occurring in heterogeneous patient populations. It affects 45–87% of critical care patients and is often associated with adverse outcomes including acquired dementia, institutionalisation, and death. Despite an exponential increase in delirium research in recent years, the pathophysiological mechanisms resulting in the clinical presentation of delirium are still hypotheses. Efforts have been made to categorise the delirium spectrum into clinically meaningful subgroups (subphenotypes), using psychomotor subtypes such as hypoactive, hyperactive, and mixed, for example, and also inflammatory and non-inflammatory delirium. Delirium remains, however, a constellation of symptoms resulting from a variety of risk factors and precipitants with currently no successful targeted pharmacological treatment. Identifying specific clinical and biological subphenotypes will greatly improve understanding of the relationship between the clinical symptoms and the putative pathways and thus risk factors, precipitants, natural history, and biological mechanism. This will facilitate risk factor mitigation, identification of potential methods for interventional studies, and informed patient and family counselling. Here, we review evidence to date and propose a framework to identify subphenotypes. Endotype identification may be done by clustering symptoms with their biological mechanism, which will facilitate research of targeted treatments. In order to achieve identification of delirium subphenotypes, the following steps must be taken: (1) robust records of symptoms must be kept at a clinical level. (2) Global collaboration must facilitate large, heterogeneous research cohorts. (3) Patients must be clustered for identification, validation, and mapping of subphenotype stability.

Spatial anxiety (i.e., feelings of apprehension and fear about navigating everyday environments) can adversely impact people’s ability to reach desired locations and explore unfamiliar places. Prior research has either assessed spatial anxiety as an individual-difference variable or measured it as an outcome, but there are currently no experimental inductions to investigate its causal effects. To address this lacuna, we developed a novel protocol for inducing spatial anxiety within a virtual environment. Participants first learnt a route using directional arrows. Next, we removed the directional arrows and randomly assigned participants to navigate either the same route ( n = 22; control condition) or a variation of this route in which we surreptitiously introduced unfamiliar paths and landmarks ( n = 22; spatial-anxiety condition). The manipulation successfully induced transient (i.e., state-level) spatial anxiety and task stress but did not significantly reduce task enjoyment. Our findings lay the foundation for an experimental paradigm that will facilitate future work on the causal effects of spatial anxiety in navigational contexts. The experimental task is freely available via the Open Science Framework ( https://osf.io/uq4v7/ ).

Artificial lights at night cause high mortality of seabirds, one of the most endangered groups of birds globally. Fledglings of burrow-nesting seabirds, and to a lesser extent adults, are attracted to and then grounded (i.e., forced to land) by lights when they fly at night. We reviewed the current state of knowledge of seabird attraction to light to identify information gaps and propose measures to address the problem. Although species in families such as Alcidae and Anatidae can be grounded by artificial light, the most affected seabirds are petrels and shearwaters (Procellariiformes). At least 56 species of Procellariiformes, more than one-third of them (24) threatened, are subject to grounding by lights. Seabirds grounded by lights have been found worldwide, mainly on oceanic islands but also at some continental locations. Petrel breeding grounds confined to formerly uninhabited islands are particularly at risk from light pollution due to tourism and urban sprawl. Where it is impractical to ban external lights, rescue programs of grounded birds offer the most immediate and employed mitigation to reduce the rate of light-induced mortality and save thousands of birds every year. These programs also provide useful information for seabird management. However, these data are typically fragmentary, biased, and uncertain and can lead to inaccurate impact estimates and poor understanding of the phenomenon of seabird attraction to lights. We believe the most urgently needed actions to mitigate and understand light-induced mortality of seabirds are estimation of mortality and effects on populations; determination of threshold light levels and safe distances from light sources; documentation of the fate of rescued birds; improvement of rescue campaigns, particularly in terms of increasing recovery rates and level of care; and research on seabird-friendly lights to reduce attraction. Las luces artificiales nocturnas causan una mortalidad alta de aves marinas, uno de los grupos de aves en mayor peligro de extinción a nivel mundial Lospolluelos de aves marinas que anidan en madrigueras, y en menor medida los adultos, son atraídos y forzados a aterrizar por las luces cuando vuelan de noche. Revisamos el estado actual del conocimiento sobre la atracción de las aves marinas por la luz para identificar vacíos de información y proponer medidas para resolver el problema. Aunque las especies de familias como Alcidae y Anatidae pueden ser forzadas a aterrizar por la luz artificial, las aves marinas más afectadas son los petreles y las pardelas (Procellariiformes). Por lo menos 56 especies de Procellariiformes, más de un tercio (24) de ellas amenazadas, son propensas al aterrizaje atraídas por las luces. Las aves marinas forzadas a aterrizar han sido halladas en todo el mundo, principalmente en islas oceánicas, pero también en algunas localidades continentales. Los sitios de anidación de los petreles confinados anteriormente a islas deshabitadas están particularmente en riesgo de sufrir contaminación lumínica debido al turismo y al crecimiento urbano. En donde no es práctico prohibir las luces externas, los programas de rescate de las aves accidentadas ofrecen la mitigación más inmediata y empleada para reducir la tasa de mortalidad inducida por la luz y salvar a miles de aves cada año. Estos programas también proporcionan información útil para el manejo de aves marinas. Sin embargo, estos datos están típicamente fragmentados, sesgados y son inciertos, y pueden llevar a estimaciones inexactas del impacto y a un entendimiento pobre del fenómeno de la atracción de las aves marinas por la luz. Creemos que las acciones necesarias de mayor urgencia para mitigar y entender la mortalidad de aves marinas producida por la luz son: la estimación de la mortalidad y los efectos sobre la población; la determinación de umbrales de niveles de luz y de distancias seguras a las fuentes de luz; el estudio del destino de las aves rescatadas; la mejora de las campañas de rescate, particularmente en términos de incrementar las tasas de recogida y el nivel de cuidado; y la investigación sobre las características de la luz para reducir la atracción de las aves marinas.

This Dutch study is a qualitative interview study. It aims to contribute to our understanding of the day-to-day experiences by providing an idiographic description of what it means existentially to be in the world as a person affected by a form of dementia, taking into account the contextual nature of these embodied experiences. We used a combination of narrative accounts of people from dementia. We first collected 322 recorded messages of 16 diarists who joined the Dutch Dementia Diaries project. This data was supplemented with 37 interview accounts. Our data analysis was inspired by Van Manen's existential phenomenological approach. The findings show that living with dementia-from a first-person perspective-can be understood as a severely unsettling experience: the people concerned enter a very uncertain, unpredictable and ambiguous period of life. They have to face all kinds of losses that considerably change and disrupt their relationships with 1) their own body, 2) with others and 3) with the surrounding world. This experience is explicated in the following themes: 1a) scrutinizing your disrupted body; 1b) trying to control your bodily loss-of-control; 2a) feeling scrutinized by the suspicious gaze of others; 2b) drifting away from significant others; 2c) having difficulties sharing the struggle; 2d) longing to be taken seriously; 2e) engaging in a world of peers; and 3a) sensing disorientation in an alien place; 3b) feeling closed in within a shrinking space; 3c) trying to control a dreaded future; 3d) trying to control a dreaded future by means of euthanasia. Our study demonstrates how the people with dementia are affected by 'the eyes of others'. They longed for a safe and accepting environment, but quite often felt scrutinized by inquisitive and disapproving looks. The outcomes also reveal a connection between dominant social imaginaries and people's self-understanding of dementia. Much of the suffering stems from living under the shadow of negative imaginaries. Furthermore, our study supports the demand for a socio-relational approach by demonstrating that-from a first-person perspective-dementia can be seen a disorder that is related in particular to questions about selfhood, social relations and social roles. For the people involved, instead of what dementia is, the focus is on what Alzheimer's disease means and does and how it affects daily life.

Data presented last month at the annual meeting of the American College of Chest Physicians by scientists at the Vanderbilt University Medical Center in Nashville, Tennessee, showed that 55% of the 2,000 people they tracked who were treated for COVID-19 in intensive-care units (ICUs) around the world had developed delirium. The pandemic has sparked physicians' interest in the condition, says Sharon Inouye, a geriatrician at the Marcus Institute for Aging and Harvard Medical School in Boston, who has studied delirium for more than 30 years. In the past decade, long-term studies have revealed that a single episode of delirium can increase the risk of developing dementia years later3, and accelerate rates of cognitive decline in those who already have the condition4. Pre-existing vulnerabilities such as chronic disease or cognitive impairment can combine with precipitating factors including surgery, anaesthesia or overwhelming infection to cause a sudden onset of confusion, disorientation and attention difficulties, especially in older adults5. [...]work8 by a team of Brazilian scientists showed that, in a group of309 people with an average age of 78 years, 32% of those who developed delirium in hospital progressed to having dementia, compared with just 16% of those who did not become delirious (see 'Delirium and cognitive decline').

Osteoarthritis (OA) has often regarded as a disease of articular cartilage only. New evidence has shifted the paradigm towards a system biology approach, where also the surrounding tissue, especially bone is studied more vigorously. However, the histological features of subchondral bone are only poorly characterized in current histological grading scales of OA. The aim of this study is to specifically characterize histological changes occurring in subchondral bone at different stages of OA and propose a simple grading system for them. 20 patients undergoing total knee replacement surgery were randomly selected for the study and series of osteochondral samples were harvested from the tibial plateaus for histological analysis. Cartilage degeneration was assessed using the standardized OARSI grading system, while a novel four-stage grading system was developed to illustrate the changes in subchondral bone. Subchondral bone histology was further quantitatively analyzed by measuring the thickness of uncalcified and calcified cartilage as well as subchondral bone plate. Furthermore, internal structure of calcified cartilage-bone interface was characterized utilizing local binary patterns (LBP) based method. The histological appearance of subchondral bone changed drastically in correlation with the OARSI grading of cartilage degeneration. As the cartilage layer thickness decreases the subchondral plate thickness and disorientation, as measured with LBP, increases. Calcified cartilage thickness was highest in samples with moderate OA. The proposed grading system for subchondral bone has significant relationship with the corresponding OARSI grading for cartilage. Our results suggest that subchondral bone remodeling is a fundamental factor already in early stages of cartilage degeneration.

In the last decade, several cases affected by Developmental Topographical Disorientation (DTD) have been described. DTD consists of a neurodevelopmental disorder affecting the ability to orient in the environment despite well-preserved cognitive functions, and in the absence of a brain lesion or other neurological or psychiatric conditions. Described cases showed different impairments in navigational skills ranging from topographic memory deficits to landmark agnosia. All cases lacked a mental representation of the environment that would allow them to use high-order spatial orientation strategies. In addition to the single case studies, a group study performed in Canada showed that the disorder is more widespread than imagined. The present work intends to investigate the occurrence of the disorder in 1,698 young Italian participants. The sample is deliberately composed of individuals aged between 18 and 35 years to exclude people who could manifest the loss of the ability to navigate as a result of an onset of cognitive decline. The sample was collected between 2016 and 2019 using the Qualtrics platform, by which the Familiarity and Spatial Cognitive Style Scale and anamnestic interview were administered. The data showed that the disorder is present in 3% of the sample and that the sense of direction is closely related to town knowledge, navigational strategies adopted, and gender. In general, males use more complex navigational strategies than females, although DTD is more prevalent in males than in females, in line with the already described cases. Finally, the paper discusses which protective factors can reduce DTD onset and which intervention measures should be implemented to prevent the spread of navigational disorders, which severely impact individuals’ autonomy and social relationships.

The antihistamine clemastine inhibits multiple stages of the Plasmodium parasite that causes malaria, but the molecular targets responsible for its parasite inhibition were unknown. Here, we applied parallel chemoproteomic platforms to discover the mechanism of action of clemastine and identify that clemastine binds to the Plasmodium falciparum TCP-1 ring complex or chaperonin containing TCP-1 (TRiC/CCT), an essential heterooligomeric complex required for de novo cytoskeletal protein folding. Clemastine destabilized all eight P. falciparum TRiC subunits based on thermal proteome profiling (TPP). Further analysis using stability of proteins from rates of oxidation (SPROX) revealed a clemastine-induced thermodynamic stabilization of the Plasmodium TRiC delta subunit, suggesting an interaction with this protein subunit. We demonstrate that clemastine reduces levels of the major TRiC substrate tubulin in P. falciparum parasites. In addition, clemastine treatment leads to disorientation of Plasmodium mitotic spindles during the asexual reproduction and results in aberrant tubulin morphology suggesting protein aggregation. This clemastine-induced disruption of TRiC function is not observed in human host cells, demonstrating a species selectivity required for targeting an intracellular human pathogen. Our findings encourage larger efforts to apply chemoproteomic methods to assist in target identification of antimalarial drugs and highlight the potential to selectively target Plasmodium TRiC-mediated protein folding for malaria intervention.