A discrete choice experiment exploring farmer preferences for insurance against extreme weather events.

Agriculture represents one of the most vulnerable sectors to extreme weather events that are projected to increase with climate change. Insurance has been advocated as a more efficient means to ensure financial security to farmers, than post-disaster aid for damages. A potential drawback of insurance however, is that unless carefully designed it could dis-incentivise farmers to engage in wider farm adaptation measures or lead to more risk-taking behaviour. This paper analyses the attractiveness of publicly-backed climate risk insurance offerings to farmers and explores their preferences for elements of insurance schemes that do not negatively affect incentives for wider farm adaptation. Specifically, a discrete choice experiment is used to reveal Irish farmers' preferences for multi-annual insurance contracts and weather-indexed versus traditional indemnity insurance and cost. Results indicate that a majority of farmers are willing to buy publicly-backed insurance for protection from extreme weather events. Younger farmers, farmers who currently have farm insurance, farmers from certain geographical locations and farmers who have been previously affected by extreme weather events are more likely to buy insurance. With respect to the design of insurance schemes, farmers prefer multi-annual coverage versus annual renewal. They also prefer indexed-insurance and have a strong preference for cheaper coverage. Despite the important role that insurance could play in protecting farms financially from damage caused by extreme weather events, few studies have examined preference for weather-indexed insurance within a European context. New evidence on farmer preferences and intended behaviours is therefore critical to inform policy in this area.

Cognitive Outcomes in Autosomal-Dominant Alzheimer's Disease: A Comprehensive Review from a Colombian Kindred with the Presenilin-1 E280A Mutation.

Background: The largest identified kindred worldwide with a single mutation causing autosomal-dominant Alzheimer's disease (ADAD) is a family from Antioquia, Colombia, carrying the Presenilin-1 (PSEN1) E280A (Paisa) mutation. The majority of mutation carriers develop dementia, typically commencing in their late 30 s, with a median onset age of 49 years. Cognitive decline is a hallmark feature. Objective: This review synthesizes the existing literature on neuropsychological assessments in PSEN1 E280A mutation carriers throughout their lifespan. We provide a comprehensive overview of cognitive outcomes in this unique population. Methods: We reviewed and integrated the published research, analyzing studies on neuropsychological assessments in PSEN1 E280A carriers. Our focus was on measures of verbal, semantic, episodic, and spatial memory, and encompassed other cognitive domains such as language, attention, visuospatial memory, and executive functioning. Results: Verbal, semantic, episodic, and spatial memory emerged as the most sensitive indicators of preclinical changes in PSEN1 E280A carriers. Inconsistencies were noted in findings from tests assessing language, attention, visuospatial memory, and executive functioning, suggesting potential limitations in detecting early cognitive changes in PSEN1 mutation carriers. Specific cognitive tasks developed for this population proved effective but underutilized. Conclusions: The review underscores the importance of continued test development tailored to detect early cognitive changes in PSEN1 E280A carriers, potentially enhancing ADAD screening. Furthermore, investigating ADAD mutations in children may identify early changes in AD and enhance our understanding of neuropsychological functioning across the lifespan. This synthesis provides valuable insights for researchers, clinicians, and policymakers engaged in the study and management of ADAD.

Utilization of an artificial intelligence-enhanced, web-based application to review bile duct brushing cytologic specimens: A pilot study.

BACKGROUND: The authors previously developed an artificial intelligence (AI) to assist cytologists in the evaluation of digital whole-slide images (WSIs) generated from bile duct brushing specimens. The aim of this trial was to assess the efficiency and accuracy of cytologists using a novel application with this AI tool. METHODS: Consecutive bile duct brushing WSIs from indeterminate strictures were obtained. A multidisciplinary panel reviewed all relevant information and provided a central interpretation for each WSI as being "positive," "negative," or "indeterminate." The WSIs were then uploaded to the AI application. The AI scored each WSI as positive or negative for malignancy (i.e., computer-aided diagnosis [CADx]). For each WSI, the AI prioritized cytologic tiles by the likelihood that malignant material was present in the tile. Via the AI, blinded cytologists reviewed all WSIs and provided interpretations (i.e., computer-aided detection [CADe]). The diagnostic accuracies of the WSI evaluation via CADx, CADe, and the original clinical cytologic interpretation (official cytologic interpretation [OCI]) were compared. RESULTS: Of the 84 WSIs, 15 were positive, 42 were negative, and 27 were indeterminate after central review. The WSIs generated on average 141,950 tiles each. Cytologists using the AI evaluated 10.5 tiles per WSI before making an interpretation. Additionally, cytologists required an average of 84.1 s of total WSI evaluation. WSI interpretation accuracies for CADx (0.754; 95% CI, 0.622-0.859), CADe (0.807; 95% CI, 0.750-0.856), and OCI (0.807; 95% CI, 0.671-0.900) were similar. CONCLUSIONS: This trial demonstrates that an AI application allows cytologists to perform a triaged review of WSIs while maintaining accuracy.

Reduced visual context effects in global motion processing in depression.

Research supports abnormal inhibitory visual motion processing in adults with remitted and current depression, but all studies to date have used paradigms with simple grating stimuli. Global motion processing, where multiple motion signals must be integrated, has not been explored in depression, nor have inhibitory processes within that domain. Depressed participants (n = 46) and healthy controls (n = 28) completed a direction discrimination task featuring a random dot pattern stimulus. Various signal (rightward or leftward dots) to noise (dots with randomly assigned directions) ratios modulated task difficulty. Metrics of global center surround suppression and facilitation were calculated. Accuracy in the baseline condition (i.e., no surrounding annulus) was not significantly different between depressed and healthy participants. Global center surround suppression and facilitation were not significantly different between healthy and depressed participants overall. When limiting the sample to unmedicated individuals, depressed participants (n = 27) showed a reduced global center surround suppression effect compared to controls, and there was no difference in global center surround facilitation. While global motion processing is intact in depression, abnormal center surround suppression effects in depression do extend to global motion stimuli. These alterations may be mitigated by the psychotropic medications taken by some subjects in our depressed sample. Future studies should explore the mechanisms underlying these effects.

The role of health systems factors in facilitating access to psychotropic medicines: a cross-sectional analysis of the WHO-AIMS in 63 low- and middle-income countries.

BACKGROUND: Neuropsychiatric conditions comprise 14% of the global burden of disease and 30% of all noncommunicable disease. Despite the existence of cost-effective interventions, including administration of psychotropic medicines, the number of persons who remain untreated is as high as 85% in low- and middle-income countries (LAMICs). While access to psychotropic medicines varies substantially across countries, no studies to date have empirically investigated potential health systems factors underlying this issue. METHODS AND FINDINGS: This study uses a cross-sectional sample of 63 LAMICs and country regions to identify key health systems components associated with access to psychotropic medicines. Data from countries that completed the World Health Organization Assessment Instrument for Mental Health Systems (WHO-AIMS) were included in multiple regression analyses to investigate the role of five major mental health systems domains in shaping medicine availability and affordability. These domains are: mental health legislation, human rights implementations, mental health care financing, human resources, and the role of advocacy groups. Availability of psychotropic medicines was associated with features of all five mental health systems domains. Most notably, within the domain of mental health legislation, a comprehensive national mental health plan was associated with 15% greater availability; and in terms of advocacy groups, the participation of family-based organizations in the development of mental health legislation was associated with 17% greater availability. Only three measures were related with affordability of medicines to consumers: level of human resources, percentage of countries' health budget dedicated to mental health, and availability of mental health care in prisons. Controlling for country development, as measured by the Human Development Index, health systems features were associated with medicine availability but not affordability. CONCLUSIONS: Results suggest that strengthening particular facets of mental health systems might improve availability of psychotropic medicines and that overall country development is associated with affordability.

Reduced cognitive control of a visually bistable image in schizophrenia.

Schizophrenia is associated with the inability to control and coordinate thoughts, actions, and perceptions. In conventional assessments of cognitive control, multiple sensory features of stimuli are concomitantly manipulated, introducing a confounding role of bottom-up perceptual information. To overcome this difficulty, we used an ambiguous visual stimulus (Necker cube), which allowed measurement of cognitive control with constant sensory input. Subjects (20 patients, 20 controls) were asked to control their perception of a transparent Necker cube by keeping a designated plane at the front or back of the stimulus, the position of which is perceptually bistable. Patients were highly deficient at controlling their perception of the cube. When a visual feature (the luminance contrast between a designated cube plane and the other planes) was systematically manipulated, an interaction was found whereby schizophrenia patients no longer under-performed on the highest contrast condition. These results show patients' impairment of controlling perception in the absence of visual modulation and suggest the potential utility of perceptually based approaches to cognitive remediation in schizophrenia.

Perceptual training strongly improves visual motion perception in schizophrenia.

Schizophrenia patients exhibit perceptual and cognitive deficits, including in visual motion processing. Given that cognitive systems depend upon perceptual inputs, improving patients' perceptual abilities may be an effective means of cognitive intervention. In healthy people, motion perception can be enhanced through perceptual learning, but it is unknown whether this perceptual plasticity remains in schizophrenia patients. The present study examined the degree to which patients' performance on visual motion discrimination can be improved, using a perceptual learning procedure. While both schizophrenia patients and healthy controls showed decreased direction discrimination thresholds (improved performance) with training, the magnitude of the improvement was greater in patients (47% improvement) than in controls (21% improvement). Both groups also improved moderately but non-significantly on an untrained task-speed discrimination. The large perceptual training effect in patients on the trained task suggests that perceptual plasticity is robust in schizophrenia and can be applied to develop bottom-up behavioral interventions.

Visual attention toward emotional stimuli: Anxiety symptoms correspond to distinct gaze patterns.

Decades of research have established a link between emotional disorders and attentional biases for emotional stimuli, but the relationship between symptom severity and visual attention is still not fully understood. Depression has been associated with increased attention towards dysphoric stimuli and decreased attention on positive stimuli ("negativity bias"), and some studies have also shown this trend in anxiety disorders. We examined eye fixation variables in 47 participants with emotional disorders completing an emotion recognition task. Results showed that depression severity was not associated with increased fixations on dysphoric stimuli, however, higher levels of generalized anxiety predicted increased fixations in the mouth region of sad and happy faces. Higher levels of social interaction anxiety predicted reduced fixations in the eye region of happy faces. While we did not replicate the negativity bias that has been shown in prior studies, our sample was highly comorbid, indicating the need to consider comorbidity, disorder severity, and the task itself when conducting research on visual attention in clinical samples. Additionally, more attention should be paid to the mouth region of emotional faces, as it may provide more specific information regarding the visual processing of emotions.

Normal Face Detection Over a Range of Luminance Contrasts in Adolescents With Autism Spectrum Disorder.

Face recognition is impaired in autism spectrum disorders (ASDs), but the reason for this remains unclear. One possibility is that impairments in the ability to visually detect faces might be a factor. As a preliminary study in this vein, we measured face detection ability as a function of visual contrast level in 13 individuals with ASD, aged 13-18, and 18 neurotypical controls (NCs) in the same age range. We also measured contrast sensitivity, using sinusoidal grating stimuli, as a control task. Individuals with ASD did not differ from controls in face detection (p > 0.9) or contrast detection (p > 0.2) ability. Performance on contrast and face detection was significantly correlated in ASD but not in NC. Results suggest that the ability to visually detect faces is not altered in ASD overall, but that alterations in basic visual processing may affect face detection ability in some individuals with ASD.

A female advantage in basic face recognition is absent in schizophrenia.

Healthy females outperform males on face recognition tasks. Relative to healthy individuals, schizophrenia patients are impaired at face perception. Yet, it is unclear whether the female advantage found in healthy controls is preserved in females with schizophrenia. In the present study, we compared male and female patients and healthy controls on two basic face perception tasks - detection and identity discrimination. In the detection task, subjects located an upright or inverted line-drawn face (or tree) embedded within a larger line-drawing. In the identity discrimination task, subjects determined which of two side-by-side face images matched an earlier presented face image. Healthy females were significantly more accurate than healthy males on face detection, but not on identity discrimination. However, female patients were not more accurate than male patients on either task. On both upright face detection and face identity discrimination, healthy controls significantly outperformed patients. Patients' performance on face detection was closely associated with tree detection and IQ scores, as well as level of psychosis. This pattern of results suggests that a female advantage in basic face perception is no longer available in schizophrenia, and that this absence may be related to a generalized deficit factor which acts to level performance across sexes, and putative changes in sex-related neurobiological differences associated with schizophrenia.

A subchronic murine intravenous pharmacokinetic and toxicity study of Hematide™, a PEGylated peptidic erythropoiesis-stimulating agent.

The subchronic toxicity of Hematide™, a synthetic PEGylated peptidic erythropoiesis-stimulating agent (ESA), was evaluated in CD-1 mice at intravenous doses of 0, 1, 5, 25, and 125 mg/kg administered once every 3 weeks for 3 months. Hematide displayed sustained plasma levels with reduced clearance and prolonged half-lives up to 59.4 hours that translated into sustained, pronounced polycythemia, bone marrow hyperplasia, and splenic and liver extramedullary hematopoiesis. Toxicological findings were considered to be secondary to exaggerated pharmacology, rather than a direct drug effect, and included mortality at ≥25 mg/kg/dose. The no-observed-adverse-effect-level was determined to be 5 mg/kg.

Visual short-term memory relates to tau and amyloid burdens in preclinical autosomal dominant Alzheimer's disease.

BACKGROUND: Over the past decade, visual short-term memory (VSTM) binding tests have been shown to be one of the most sensitive behavioral indicators of Alzheimer's disease (AD), especially when they require the binding of multiple features (e.g., color and shape). Recently, it has become possible to directly measure amyloid and tau levels in vivo via positron emission tomography (PET). To this point, these behavioral and neurochemical markers have not been compared in humans with AD or at risk for it. METHODS: In a cross-sectional study, we compared VSTM performance to tau and amyloid concentrations, measured by PET, in individuals certain to develop AD by virtue of their inheritance of the presenilin-1 E280A mutation. These included 21 clinically unimpaired subjects and 7 subjects with early mild cognitive impairment (MCI), as well as 30 family members who were not carriers of the mutation. RESULTS: We found that VSTM performance correlated strongly with tau in entorhinal cortex and inferior temporal lobe, and also with amyloid when examining asymptomatic carriers only. The condition requiring binding was not preferentially linked to tau-in fact, the non-binding "shape only" condition showed a stronger relationship. CONCLUSIONS: The results confirm VSTM's status as an early marker of AD pathology and raise interesting questions as to the course of binding-specific versus non-binding aspects of VSTM in early AD.

Image acquisition and quality assurance in the Boston Adolescent Neuroimaging of Depression and Anxiety study.

The Connectomes Related to Human Diseases (CRHD) initiative was developed with the Human Connectome Project (HCP) to provide high-resolution, open-access, multi-modal MRI data to better understand the neural correlates of human disease. Here, we present an introduction to a CRHD project, the Boston Adolescent Neuroimaging of Depression and Anxiety (BANDA) study, which is collecting multimodal neuroimaging, clinical, and neuropsychological data from 225 adolescents (ages 14-17), 150 of whom are expected to have a diagnosis of depression and/or anxiety. Our transdiagnostic recruitment approach samples the full spectrum of depressed/anxious symptoms and their comorbidity, consistent with NIMH Research Domain Criteria (RDoC). We focused on an age range that is critical for brain development and for the onset of mental illness. This project sought to harmonize imaging sequences, hardware, and functional tasks with other HCP studies, although some changes were made to canonical HCP methods to accommodate our study population and questions. We present a thorough overview of our imaging sequences, hardware, and scanning protocol. We detail similarities and differences between this study and other HCP studies. We evaluate structural-, diffusion-, and functional-image-quality measures that may be influenced by clinical factors (e.g., disorder, symptomatology). Signal-to-noise and motion estimates from the first 140 adolescents suggest minimal influence of clinical factors on image quality. We anticipate enrollment of an additional 85 participants, most of whom are expected to have a diagnosis of anxiety and/or depression. Clinical and neuropsychological data from the first 140 participants are currently freely available through the National Institute of Mental Health Data Archive (NDA).

Visual and cognitive processing of face information in schizophrenia: detection, discrimination and working memory.

Face recognition involves several physiological and psychological processes, including those in visual, cognitive and affective domains. Studies have found that schizophrenia patients are deficient at recognizing facial emotions, yet visual and cognitive processing of facial information in this population has not been systematically examined. In this study, we examined visual detection, perceptual discrimination and working memory of faces as well as non-face visual objects in patients. Visual detection was measured by accuracy when detecting the presence of a briefly displayed face, image which contained only the basic configural information of a face. Perceptual discrimination was measured by discriminability scores for individual facial identity images, in which the degree of similarity between images was systematically varied via morphing. Working memory was measured by the discriminability scores when two comparison face images were separated by 3 or 10 s. All measurements were acquired using a psychophysical method (two-alternative forced choice). Relative to controls, patients showed significantly reduced accuracy in visual detection of faces (p=0.003), moderately degraded performance in perceptual discrimination of faces (p=0.065), and significantly impaired performance in working memory of faces (p<0.001 for both 3 and 10 sec conditions). Patients' performance on non-face versions of these tasks, while degraded, was not correlated with performance on face recognition. This pattern of results indicates that greater signal strength is required for visual and cognitive processing of facial information in schizophrenia.

A Double-Blind Placebo Controlled Study of Intranasal Oxytocin's Effect on Emotion Recognition and Visual Attention in Outpatients with Emotional Disorders.

The current study used double-blind, placebo-controlled design to examine the effect of intranasal oxytocin (OT) on emotion recognition (ER) and visual attention in 60 outpatients presenting for assessment and treatment of emotional disorders. Our primary hypothesis was that OT would improve recognition of happy faces in depressed participants. The main effect of OT on ER accuracy, speed, and proportion of fixations in the eye region was not significant. Diagnostic group (i.e., presence/absence of a depressive disorder) moderated the effect of OT on ER, but not as expected: OT significantly slowed ER speed for all emotions in participants with anxiety disorders, but did not affect performance in participants with depressive disorders. Depressed participants fixated significantly less in the eye region of sad faces than anxious participants. Before OT can be used to target ER biases, additional research is needed to explicate the differential impact of OT on ER speed in patients with anxiety versus mood disorders.

Striatal amyloid is associated with tauopathy and memory decline in familial Alzheimer's disease.

BACKGROUND: Autosomal dominant Alzheimer's disease (ADAD) is distinguished from late-onset AD by early striatal amyloid-ß deposition. To determine whether striatal Pittsburgh compound B (PiB)-PET measurements of amyloid-ß can help predict disease severity in ADAD, we compared relationships of striatal and neocortical PiB-PET to age, tau-PET, and memory performance in the Colombian Presenilin 1 E280A kindred. METHODS: Fourteen carriers (age = 28-42, Mini-Mental State Examination = 26-30) and 20 age-matched non-carriers were evaluated using PiB, flortaucipir (FTP; tau), and memory testing (CERAD Word List Learning). PiB-PET signal was measured in neocortical and striatal aggregates. FTP-PET signal was measured in entorhinal cortex. RESULTS: Compared to non-carriers, mutation carriers had age-related elevations in both neocortical and striatal PiB binding. The PiB elevation in carriers was significantly greater in the striatum than in the neocortex. In mutation carriers, PiB binding in both the neocortex and the striatum is related to entorhinal FTP; however, the association was stronger with the striatum. Only striatal PiB was associated with worse memory. Remarkably, PiB binding in the striatum, but not in the neocortex, predicted entorhinal FTP and lower memory scores after adjusting for age, indicating that striatal PiB identified the carriers with the most severe disease. CONCLUSIONS: Based on these preliminary cross-sectional findings, striatal PiB-PET measurements may offer particular value in the detection and tracking of preclinical ADAD, informing a mutation carrier's prognosis and evaluating amyloid-ß-modifying ADAD treatments.

Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease.

Chronic preclinical safety evaluation of Hematide, a pegylated peptidic erythropoiesis stimulating agent in monkeys.

Hematide is a synthetic peptide-based, pegylated erythropoiesis stimulating agent in clinical development for treatment of anemia. To support chronic clinical dosing requirements, a 9-month repeat dose IV monkey safety study was undertaken. Animals received 0, 0.2, 2 or 20 mg/kg hematide IV every three weeks for nine months followed by a 14-week recovery. Hematide administration was associated with time and dose-dependent polycythemia. Histological findings were related to exaggerated pharmacology that was secondary to the administration of an erythropoiesis stimulating agent to a normocythemic animal. In conclusion, these results support the use of repeated administration of hematide for the correction of anemia.

Inefficient face detection in schizophrenia.

BACKGROUND: Higher levels of facial processing, such as recognition of the individuality and emotional expression of faces, are abnormal in schizophrenia. It is unknown, however, whether the visual detection of a face as face is impaired as well. METHODS: We examined the performance of schizophrenia patients (n=29) and normal controls (n=28) in locating a line-drawn face on the left or the right side of a larger line drawing. To prevent the normal formation of general facial impressions, stimulus presentations were brief (13-104 ms). The face stimuli were either displayed upright or inverted in order to study the face inversion effect, ie, the specific effect of stimulus inversion on face processing. RESULTS: Schizophrenia patients showed a significantly reduced face inversion effect, resulting primarily from significantly lower accuracy in detecting upright faces than normal controls. In tree detection, a comparison task that was also administered, the stimulus inversion effect was similarly small in both groups. CONCLUSION: Given the primitive nature and brief duration of the stimuli, and the simplicity of the task, these results indicate that at the initial visual detection stage, facial processing is inefficient in schizophrenia. By isolating face detection from other aspects of face recognition, this study identifies a face-specific visual deficit in schizophrenia, which may ultimately contribute to impaired face-related cognitive and emotional processing and social interaction.