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Abstract Optical microscopy has long been the standard method for diagnosis in cytopathology. Whole slide scanners can image and digitize large sample areas automatically, but are slow, expensive and therefore not widely available. Clinical diagnosis of cytology specimens is especially challenging since these samples are both spread over large areas and thick, which requires 3D capture. Here, we introduce a new parallelized microscope for scanning thick specimens across extremely wide fields-of-view (54 × 72 mm2) at 1.2 and 0.6 μm resolutions, accompanied by machine learning software to rapidly assess these 16 gigapixel scans. This Multi-Camera Array Scanner (MCAS) comprises 48 micro-cameras closely arranged to simultaneously image different areas. By capturing 624 megapixels per snapshot, the MCAS is significantly faster than most conventional whole-slide scanners. We used this system to digitize entire cytology samples (scanning three entire slides in 3D in just several minutes) and demonstrate two machine learning techniques to assist pathologists: first, an adenocarcinoma detection model in lung specimens (0.73 recall); second, a slide-level classification model of lung smears (0.969 AUC).

Assessing the foraging ecology of a threatened species is necessary to understand their movement behaviour and habitat use patterns, which are essential for developing effective protection strategies. Here, the foraging ecology of reef manta rays (Mobula alfredi) in the Chagos Archipelago, a region encompassed by a vast no-take marine protected area (MPA), was investigated using stable isotope analysis of skin and muscle tissue. Enriched δ13C values suggest the population predominantly forages in nearshore environments. Skin δ13C values increased with increased rainfall, likely associated with the boosts in primary production and zooplankton biomass due to the coastal advection of seabird guano. Annual variations in δ13C values of skin and muscle were observed and are consistent with reduced nutrient transport associated with the effects of Indian Ocean Dipole oscillations, including a deepening of the thermocline, a suppression of cold-water upwelling, and reduced rainfall. Short- and long-term foraging strategies and locations were identified by applying hierarchical clustering, isotopic niche analysis, and Bayesian stable isotope mixing models to δ13C and δ15N of paired skin and muscle tissue samples. Two isotopically distinct groups of M. alfredi were identified, employing either local foraging strategies restricted to specific locations or wide-ranging strategies that likely mean they engage in regular migrations throughout the archipelago. Ninety-eight percent of M. alfredi were estimated to switch between strategies utilising and connecting multiple discrete nearshore habitats, emphasising their role in ecosystem functioning by facilitating the transport of nutrients across ecosystem boundaries. However, illegal, unreported, and unregulated fishing and lost or abandoned fishing gear commonly occur within the MPA. Locations of particular concern are Egmont Atoll as it is a highly active aggregation location and Peros Banhos Atoll where IUU frequently occurs and M. alfredi are estimated to be heavily reliant upon for foraging. Frequent migrations between atolls by M. alfredi also raises concern over their vulnerability to these activities along migration corridors. This research bridges current knowledge gaps in this population's foraging ecology and concomitant movement patterns, which should inform conservation strategies in the region.

Aims. We aimed to determine whether plasma advanced glycation end products or oxidation products (AGE/oxidation-P) predict altered renal function and/or preeclampsia (PE) in pregnant women with type 1 diabetes. Methods. Prospectively, using a nested case-control design, we studied 47 pregnant women with type 1 diabetes, of whom 23 developed PE and 24 did not. Nineteen nondiabetic, normotensive pregnant women provided reference values. In plasma obtained at ~12, 22, and 32 weeks’ gestation (visits 1, 2, and 3; V1-V3), we measured five AGE products (carboxymethyllysine (CML), carboxyethyl-lysine (CEL), methylglyoxal-hydroimidazolone (MGH1), 3-deoxyglucosone hydroimidazolone (3DGH), and glyoxal-hydroimidazolone (GH1)) and four oxidation products (methionine sulfoxide (MetSO), 2-aminoadipic acid (2-AAA), 3-nitrotyrosine (3NT), and dityrosine (DT)), by liquid chromatography/mass spectroscopy. Clinical outcomes were “estimated glomerular filtration rate” (eGFR) at each visit and onset of PE. Results. In diabetic women, associations between AGE/oxidation-P and eGFR were found only in those who developed PE. In this group, CEL, MGH1, and GH1 at V2 and CML, CEL, MGH1, and GH1 at V3 were inversely associated with contemporaneous eGFR, while CEL, MGH1, 3DGH, and GH1 at V2 were inversely associated with eGFR at V3 (all p

Abstract Background The effect of personalised nutrition advice on discretionary foods intake is unknown. To date, two national classifications for discretionary foods have been derived. This study examined changes in intake of discretionary foods and beverages following a personalised nutrition intervention using these two classifications. Methods Participants were recruited into a 6-month RCT across seven European countries (Food4Me) and were randomised to receive generalised dietary advice (control) or one of three levels of personalised nutrition advice (based on diet [L1], phenotype [L2] and genotype [L3]). Dietary intake was derived from an FFQ. An analysis of covariance was used to determine intervention effects at month 6 between personalised nutrition (overall and by levels) and control on i) percentage energy from discretionary items and ii) percentage contribution of total fat, SFA, total sugars and salt to discretionary intake, defined by Food Standards Scotland (FSS) and Australian Dietary Guidelines (ADG) classifications. Results Of the 1607 adults at baseline, n = 1270 (57% female) completed the intervention. Percentage sugars from FSS discretionary items was lower in personalised nutrition vs control (19.0 ± 0.37 vs 21.1 ± 0.65; P = 0.005). Percentage energy (31.2 ± 0.59 vs 32.7 ± 0.59; P = 0.031), percentage total fat (31.5 ± 0.37 vs 33.3 ± 0.65; P = 0.021), SFA (36.0 ± 0.43 vs 37.8 ± 0.75; P = 0.034) and sugars (31.7 ± 0.44 vs 34.7 ± 0.78; P

Abstract Globally, reef manta rays (Mobula alfredi) are in decline and are particularly vulnerable to exploitation and disturbance at aggregation sites. Here, passive acoustic telemetry and a suite of advanced oceanographic technologies were used for the first time to investigate the fine‐scale (5‐min) influence of oceanographic drivers on the visitation patterns of 19 tagged M. alfredi to a feeding aggregation site at Egmont Atoll in the Chagos Archipelago. Boosted regression trees indicate that tag detection probability increased with the intrusion of cold‐water bores propagating up the atoll slope through the narrow lagoon inlet during flood tide, potentially transporting zooplankton from the thermocline. Tag detection probability also increased with warmer near‐surface temperature close to low tide, with near‐surface currents flowing offshore, and with high levels of backscatter (a proxy of zooplankton biomass). These combinations of processes support the proposition that zooplankton carried from the thermocline into the lagoon during the flood may be pumped back out through the narrow inlet during an ebb tide. These conditions provide temporally limited feeding opportunities for M. alfredi, which are tied on the tides. Results also provide some evidence of the presence of Langmuir Circulation, which transports and concentrates zooplankton, and may partly explain why M. alfredi occasionally remained at the feeding location for longer than that two hours. Identification of these correlations provides unique insight into the dynamic synthesis of fine‐scale oceanographic processes which are likely to influence the foraging ecology of M. alfredi at Egmont Atoll, and elsewhere throughout their range.

Brexit activists demonstrating outside the British Houses of Parliament were studied in situ to examine their potential for pro-group extreme behavior. This involved activists of two polarized, opposing views; those of Leave and Remain. The research engaged concepts linking the different theoretical perspectives of identity fusion and personal construct psychology. The study measured participants' degree of fusion to their group using a verbal measure. Willingness to undertake extreme acts was assessed in several ways: a measure of willingness to fight for the group, adaptations of the trolley dilemma and questions regarding political violence. Individual construing was examined using repertory grid technique and a semi-structured interview. Results were similar for both Leave and Remain participants. The majority of activists identified as “fused” to their group and, if so, were more likely to undertake hypothetical extreme behavior compared to those who did not identify as “fused.” Repertory grid technique indicated that becoming an activist provided individuals with a clearer and more positive view of themselves. Opposition activists were construed more negatively and extremely than fellow activists, and this construal was associated with an increased willingness to undertake extreme pro-group behavior. This was consistent with the personal construct model of radicalization and was heightened in those who were “fused.” Interview data provided support for the constructivist model and revealed characteristics and concerns of the two groups. Overall, the findings indicate that campaigning organizations contain fused individuals, who are more likely to undertake hypothetical pro-group violence including self-sacrifice. This has broader implications which may be particularly pertinent, given the violent impact of extremist activists around the globe.

Decreased sea ice cover in the northern Bering Sea has altered annual phytoplankton phenology owing to an expansion of open water duration and its impact on ocean stratification. Limitations of satellite remote sensing such as the inability to detect bloom activity throughout the water column, under ice, and in cloudy conditions dictate the need for shipboard based measurements to provide more information on bloom dynamics. In this study, we adapted remote sensing land cover classification techniques to provide a new means to determine bloom stage from shipboard samples. Specifically, we used multiyear satellite time series of chlorophyll a to determine whether in-situ blooms were actively growing or mature (i.e., past-peak) at the time of field sampling. Field observations of chlorophyll a and pheophytin (degraded and oxidized chlorophyll products) were used to calculate pheophytin proportions, i.e., (Pheophytin/(Chlorophyll a + Pheophytin)) and empirically determine whether the bloom was growing or mature based on remotely sensed bloom stages. Data collected at 13 north Bering Sea stations each July from 2013-2019 supported a pheophytin proportion of 28% as the best empirical threshold to distinguish a growing vs. mature bloom stage. One outcome was that low vs. high sea ice years resulted in significantly different pheophytin proportions in July; in years with low winter-to-spring ice, more blooms with growing status were observed, compared to later stage, more mature blooms following springs with abundant seasonal sea ice. The detection of growing blooms in July following low ice years suggests that changes in the timing of the spring bloom triggers cascading effects on mid-summer production.

Background Citizen science is increasingly popular and has the potential to collect extensive datasets at lower costs than traditional surveys conducted by professional scientists. Ferries have been used to collect data on cetacean populations for decades, providing long-term time series for monitoring of cetacean populations. One cetacean species of concern is the common dolphin, which has been found stranded around the north-east Atlantic in recent years, with high numbers on French coasts being attributed to fisheries bycatch. We estimate common dolphin densities in the north-east Atlantic and investigate the ability of citizen science data to identify changes in marine mammal densities and areas of importance. Materials and Methods Data were collected by citizen scientists on ferries between April and October in 2006–2017. Common dolphin sightings data from two ferry routes across three regions, Bay of Biscay (n = 569); south-west United Kingdom to the Isles of Scilly in the Celtic Sea (n = 260); and English Channel (n = 75), were used to estimate density across ferry routes. Two-stage Density Surface Models accounted for imperfect detection, and tested the influence of environmental (chlorophyll a, sea surface temperature, depth, and slope), spatial (latitude and longitude) and temporal terms (year and Julian day) on occurrence. Results Overall detection probability was highest in the areas sampled within the English Channel (0.384) and Bay of Biscay (0.348), and lowest on the Scilly’s route (0.158). Common dolphins were estimated to occur in higher densities on the Scilly’s route (0.400 per km2) and the Bay of Biscay (0.319 per km2), with low densities in the English Channel (0.025 per km2). Densities on the Scilly’s route appear to have been relatively stable since 2006 with a slight decrease in 2017. Densities peaked in the Bay of Biscay in 2013 with lower numbers since. Densities in the English Channel appear to have increased over time since 2009. Discussion This study highlights the effectiveness of citizen science data to investigate the distribution and density of cetaceans. The densities and temporal changes shown by this study are representative of those from wider-ranging robust estimates. We highlight the ability of citizen science to collect data over extensive periods of time which complements dedicated, designed surveys. Such long-term data are important to identify changes within a population; however, citizen science data may, in some situations, present challenges. We provide recommendations to ensure high-quality data which can be used to inform management and conservation of cetacean populations.

Abstract Background National guidelines emphasize healthy eating to promote wellbeing and prevention of non-communicable diseases. The perceived healthiness of food is determined by many factors affecting food intake. A positive perception of healthy eating has been shown to be associated with greater diet quality. Internet-based methodologies allow contact with large populations. Our present study aims to design and evaluate a short nutritional perception questionnaire, to be used as a screening tool for assessing nutritional status, and to predict an optimal level of personalisation in nutritional advice delivered via the Internet. Methods Data from all participants who were screened and then enrolled into the Food4Me proof-of-principle study (n = 2369) were used to determine the optimal items for inclusion in a novel screening tool, the Nutritional Perception Screening Questionnaire-9 (NPSQ9). Exploratory and confirmatory factor analyses were performed on anthropometric and biochemical data and on dietary indices acquired from participants who had completed the Food4Me dietary intervention (n = 1153). Baseline and intervention data were analysed using linear regression and linear mixed regression, respectively. Results A final model with 9 NPSQ items was validated against the dietary intervention data. NPSQ9 scores were inversely associated with BMI (β = −0.181, p

The risk for preeclampsia (PE) is enhanced ~4-fold by the presence of maternal type 1 diabetes (T1DM). Vitamin D is essential for healthy pregnancy. We assessed the total, bioavailable, and free concentrations of plasma 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and vitamin D binding protein (VDBP) at ~12, ~22, and ~32 weeks’ gestation (“Visits” (V) 1, 2, and 3, respectively) in 23 T1DM women who developed PE, 24 who remained normotensive, and 19 non-diabetic, normotensive women (reference controls). 25(OH)D deficiency was more frequent in diabetic than non-diabetic women (69% vs. 22%, p < 0.05), but no measure of 25(OH)D predicted PE. By contrast, higher 1,25(OH)2D concentrations at V2 (total, bioavailable, and free: p < 0.01) and V3 (bioavailable: p < 0.05; free: p < 0.01), lower concentrations of VDBP at V3 (p < 0.05), and elevated ratios of 1,25(OH)2D/VDBP (V2, V3: p < 0.01) and 1,25(OH)2D/25(OH)D (V3, p < 0.05) were all associated with PE, and significance persisted in multivariate analyses. In summary, in women with T1DM, concentrations of 1,25(OH)2D were higher, and VDBP lower, in the second and third trimesters in women who later developed PE than in those who did not. 1,25(OH)2D may serve as a new marker for PE risk and could be implicated in pathogenesis.

Diet-quality scores (DQS), which are developed across the globe, are used to define adherence to specific eating patterns and have been associated with risk of coronary heart disease and type-II diabetes. We explored the association between five diet-quality scores (Healthy Eating Index, HEI; Alternate Healthy Eating Index, AHEI; MedDietScore, MDS; PREDIMED Mediterranean Diet Score, P-MDS; Dutch Healthy Diet-Index, DHDI) and markers of metabolic health (anthropometry, objective physical activity levels (PAL), and dried blood spot total cholesterol (TC), total carotenoids, and omega-3 index) in the Food4Me cohort, using regression analysis. Dietary intake was assessed using a validated Food Frequency Questionnaire. Participants (n = 1480) were adults recruited from seven European Union (EU) countries. Overall, women had higher HEI and AHEI than men (p < 0.05), and scores varied significantly between countries. For all DQS, higher scores were associated with lower body mass index, lower waist-to-height ratio and waist circumference, and higher total carotenoids and omega-3-index (p trends < 0.05). Higher HEI, AHEI, DHDI, and P-MDS scores were associated with increased daily PAL, moderate and vigorous activity, and reduced sedentary behaviour (p trend < 0.05). We observed no association between DQS and TC. To conclude, higher DQS, which reflect better dietary patterns, were associated with markers of better nutritional status and metabolic health.

Growing concerns about climate change and energy security have fueled a rapid increase in the development of marine renewable energy installations (MREIs). The potential ecological consequences of increased use of these devices emphasizes the need for high quality environmental impact assessment (EIA). We demonstrate that these processes are hampered severely, primarily because ambiguities in the legislation and lack of clear implementation guidance are such that they do not ensure robust assessment of the significance of impacts and cumulative effects. We highlight why the regulatory framework leads to conceptual ambiguities and propose changes which, for the most part, do not require major adjustments to standard practice. We emphasize the importance of determining the degree of confidence in impacts to permit the likelihood as well as magnitude of impacts to be quantified and propose ways in which assessment of population-level impacts could be incorporated into the EIA process. Overall, however, we argue that, instead of trying to ascertain which particular developments are responsible for tipping an already heavily degraded marine environment into an undesirable state, emphasis should be placed on better strategic assessment.

Mediterranean Diet (MedDiet) adherence has been proven to produce numerous health benefits. In addition, nutrigenetic studies have explained some individual variations in the response to specific dietary patterns. The present research aimed to explore associations and potential interactions between MedDiet adherence and genetic background throughout the Food4Me web-based nutritional intervention. Dietary, anthropometrical and biochemical data from volunteers of the Food4Me study were collected at baseline and after 6 months. Several genetic variants related to metabolic risk features were also analysed. A Genetic Risk Score (GRS) was derived from risk alleles and a Mediterranean Diet Score (MDS), based on validated food intake data, was estimated. At baseline, there were no interactions between GRS and MDS categories for metabolic traits. Linear mixed model repeated measures analyses showed a significantly greater decrease in total cholesterol in participants with a low GRS after a 6-month period, compared to those with a high GRS. Meanwhile, a high baseline MDS was associated with greater decreases in Body Mass Index (BMI), waist circumference and glucose. There also was a significant interaction between GRS and the MedDiet after the follow-up period. Among subjects with a high GRS, those with a high MDS evidenced a highly significant reduction in total carotenoids, while among those with a low GRS, there was no difference associated with MDS levels. These results suggest that a higher MedDiet adherence induces beneficial effects on metabolic outcomes, which can be affected by the genetic background in some specific markers.

Malate, the tricarboxylic acid (TCA) cycle metabolite, increased lifespan and thermotolerance in the nematode C. elegans. Malate can be synthesized from fumarate by the enzyme fumarase and further oxidized to oxaloacetate by malate dehydrogenase with the accompanying reduction of NAD. Addition of fumarate also extended lifespan, but succinate addition did not, although all three intermediates activated nuclear translocation of the cytoprotective DAF-16/FOXO transcription factor and protected from paraquat-induced oxidative stress. The glyoxylate shunt, an anabolic pathway linked to lifespan extension in C. elegans, reversibly converts isocitrate and acetyl-CoA to succinate, malate, and CoA. The increased longevity provided by malate addition did not occur in fumarase (fum-1), glyoxylate shunt (gei-7), succinate dehydrogenase flavoprotein (sdha-2), or soluble fumarate reductase F48E8.3 RNAi knockdown worms. Therefore, to increase lifespan, malate must be first converted to fumarate, then fumarate must be reduced to succinate by soluble fumarate reductase and the mitochondrial electron transport chain complex II. Reduction of fumarate to succinate is coupled with the oxidation of FADH2 to FAD. Lifespan extension induced by malate depended upon the longevity regulators DAF-16 and SIR-2.1. Malate supplementation did not extend the lifespan of long-lived eat-2 mutant worms, a model of dietary restriction. Malate and fumarate addition increased oxygen consumption, but decreased ATP levels and mitochondrial membrane potential suggesting a mild uncoupling of oxidative phosphorylation. Malate also increased NADPH, NAD, and the NAD/NADH ratio. Fumarate reduction, glyoxylate shunt activity, and mild mitochondrial uncoupling likely contribute to the lifespan extension induced by malate and fumarate by increasing the amount of oxidized NAD and FAD cofactors.

To learn a verb, children must attend to objects and relations, often within a dynamic scene. Several studies show that comparing varied events linked to a verb helps children learn verbs, but there is also controversy in this area. This study asks whether children benefit from seeing variation across events as they learn a new verb, and uses an eye tracker to test whether children adjust their visual attention to specific objects to better understand how they may be comparing events to each other. Children saw events in which the tool varied, the affected object varied, or there was no variation (control). No prior verb study has tested children's visual attention to specific objects under different variability conditions. We found 2½- and 3½-year-olds could extend verbs, and they were more successful with age. Analyses of the looking patterns in the learning phase show that children's attention to specific objects in events varied by condition, and that reduced looking to the tool was linked to less success at test. Eye tracking can provide a more detailed view of what children attend to while learning a new verb, which should help us better understand how children are learning from variation across examples.

Predictive models are central to many scientific disciplines and vital for informing management in a rapidly changing world. However, limited understanding of the accuracy and precision of models transferred to novel conditions (their 'transferability') undermines confidence in their predictions. Here, 50 experts identified priority knowledge gaps which, if filled, will most improve model transfers. These are summarized into six technical and six fundamental challenges, which underlie the combined need to intensify research on the determinants of ecological predictability, including species traits and data quality, and develop best practices for transferring models. Of high importance is the identification of a widely applicable set of transferability metrics, with appropriate tools to quantify the sources and impacts of prediction uncertainty under novel conditions.

AbstractIn May 2021, four months after the fatal insurrection of the “Save America” rally at Capitol Hill, 420 supporters of Donald Trump participated in an online study. Although it was not possible to recruit specifically for those involved, a subsample reported being present and active in the insurrection (n = 38), with several involved in the storming of the Capitol Building (n = 28). Individuals’ construing was examined through the repertory grid technique, combined with measures of fusion to the group and willingness to undertake hypothetical extreme pro-group actions. Relatively low cognitive complexity was observed in those actually or hypothetically willing to be involved in the most extreme actions, suggesting that they were the least able to adapt to the world around them. A more positive and meaningful view of the self was developed on becoming a Trump supporter, and fellow Trump supporters were construed more positively than anti-Trump activists. Repertory grid and fusion scores were associated with both actual and hypothetical extreme action. Findings assist in the advancement of understanding why some individuals undertake extreme acts on behalf of a political leader, whilst others do not. With political environments becoming increasingly polarized around the globe, such knowledge is vital. [ABSTRACT FROM AUTHOR]

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