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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]

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 < 0.05). There were no associations of plasma AGE or oxidation-P with pregnancy-related development of proteinuria or PE. Conclusions. Inverse associations of second and early third trimester plasma AGE with eGFR among type 1 diabetic women who developed PE suggest that these patients constitute a subset susceptible to AGE-mediated injury and thus to cardiorenal complications later in life. However, AGE/oxidation-P did not predict PE in type 1 diabetic women. [ABSTRACT FROM AUTHOR]

Purpose: The Child Health Utility-9 Dimensions (CHU9D) is a patient-reported outcome measure to generate Quality-Adjusted Life Years (QALYs), recommended for economic evaluations of interventions to inform funding decisions. When the CHU9D is not available, mapping algorithms offer an opportunity to convert other paediatric instruments, such as the Paediatric Quality of Life Inventory™ (PedsQL), onto the CHU9D scores. This study aims to validate current PedsQL to CHU9D mappings in a sample of children and young people of a wide age range (0 to 16 years of age) and with chronic conditions. New algorithms with improved predictive accuracy are also developed. Methods: Data from the Children and Young People's Health Partnership (CYPHP) were used (N = 1735). Four regression models were estimated: ordinal least squared, generalized linear model, beta-binomial and censored least absolute deviations. Standard goodness of fit measures were used for validation and to assess new algorithms. Results: While previous algorithms perform well, performance can be enhanced. OLS was the best estimation method for the final equations at the total, dimension and item PedsQL scores levels. The CYPHP mapping algorithms include age as an important predictor and more non-linear terms compared with previous work. Conclusion: The new CYPHP mappings are particularly relevant for samples with children and young people with chronic conditions living in deprived and urban settings. Further validation in an external sample is required. Trial registration number NCT03461848; pre-results. [ABSTRACT FROM AUTHOR]

Immobilization of porphyrin complexes into crystalline metal–organic frameworks (MOFs) enables high exposure of porphyrin active sites for CO2 electroreduction. Herein, well‐dispersed iron‐porphyrin‐based MOF (PCN‐222(Fe)) on carbon‐based electrodes revealed optimal turnover frequencies for CO2 electroreduction to CO at 1 wt.% catalyst loading, beyond which the intrinsic catalyst activity declined due to CO2 mass transport limitations. In situ Raman suggested that PCN‐222(Fe) maintained its structure under electrochemical bias, permitting mechanistic investigations. These revealed a stepwise electron transfer‐proton transfer mechanism for CO2 electroreduction on PCN‐222(Fe) electrodes, which followed a shift from a rate‐limiting electron transfer to CO2 mass transfer as the potential increased from −0.6 V to −1.0 V vs. RHE. Our results demonstrate how intrinsic catalytic investigations and in situ spectroscopy are needed to elucidate CO2 electroreduction mechanisms on PCN‐222(Fe) MOFs. [ABSTRACT FROM AUTHOR]

Immobilization of porphyrin complexes into crystalline metal–organic frameworks (MOFs) enables high exposure of porphyrin active sites for CO2 electroreduction. Herein, well‐dispersed iron‐porphyrin‐based MOF (PCN‐222(Fe)) on carbon‐based electrodes revealed optimal turnover frequencies for CO2 electroreduction to CO at 1 wt.% catalyst loading, beyond which the intrinsic catalyst activity declined due to CO2 mass transport limitations. In situ Raman suggested that PCN‐222(Fe) maintained its structure under electrochemical bias, permitting mechanistic investigations. These revealed a stepwise electron transfer‐proton transfer mechanism for CO2 electroreduction on PCN‐222(Fe) electrodes, which followed a shift from a rate‐limiting electron transfer to CO2 mass transfer as the potential increased from −0.6 V to −1.0 V vs. RHE. Our results demonstrate how intrinsic catalytic investigations and in situ spectroscopy are needed to elucidate CO2 electroreduction mechanisms on PCN‐222(Fe) MOFs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Observational studies link high whole grain intakes to reduced risk of many chronic diseases. This study quantified whole grain intakes in the Irish adult population and examined the major contributing sources. It also investigated potential dietary strategies to improve whole grain intakes. Methods: Whole grain intakes were calculated in a nationally representative sample of 1500 Irish adults using data from the most recent national food survey, the National Adult Nutrition Survey (NANS). Food consumption was assessed, at brand level where possible, using a 4-day semi-weighed food diary with whole grain content estimated from labels on a dry matter basis. Results: Mean daily whole grain intakes were 27.8 ± 29.4 g/day, with only 19% of the population meeting the quantity-specific recommendation of 48 g per day. Wheat was the highest contributor to whole grain intake at 66%, followed by oats at 26%. High whole grain intakes were associated with higher dietary intakes of fibre, magnesium, potassium, phosphorus, and a higher alternative Mediterranean Diet Score. Whole grain foods were most frequently eaten at breakfast time. Regression analysis revealed that consumption of an additional 10 g of whole grain containing 'ready-to-eat breakfast cereals', 'rice or pastas', or 'breads' each day would increase intake of whole grains by an extra 5, 3.5, and 2.7 g, respectively. Conclusions: This study reveals low intakes of whole grains in Irish adults. Recommending cereals, breads, and grains with higher whole grain content as part of public health campaigns could improve whole grain intakes. [ABSTRACT FROM AUTHOR]

Examines the difficulties and implications of outsourcing the catalog department by drawing on parallels between outsourcing in business and in libraries. Mechanism of outsourcing; Assumptions about outsourcing; Successful outsourcing; Reason for outsourcing cataloging; Beyond total outsourcing.

Explores the difficulties encountered in romanizing Chinese and Japanese scripts with recommendations for a separate East Asian collection. Romanized access through a Latin-script catalog; Nonromanized access through a browsing collection; Non-phonetic script; Intonation; Multisyllabic words; Romanization systems; Kanji; Katakana and hiragana; Access options.

Since the inception of hemodialysis (HD) for patients with chronic kidney disease, the "perfect" dialysis prescription has remained elusive. Part of this may relate to the heterogeneity among populations, individual patients, and differences in access to health provision. The optimal balance between dialysis frequency and duration to achieve reductions in patient morbidity and mortality continues to be debated. The concept of dialysis adequacy originated from a post hoc mathematical analysis of the National Cooperative Study and has evolved to become a way of calculating dialysis dose and standardizing the dialysis prescription. In contrast, in its originally conceived sense, dialysis adequacy referred to the effective clearance of small solutes. Given the evolution of dialysis practice, we now aim to consider dialysis adequacy in a broader and more holistic manner particularly in view of our aging population and focus toward important patient-centered outcomes. While the traditional thrice weekly, HD regimen remains the default renal replacement modality, alternative strategies including short daily HD, long conventional HD, and long nocturnal HD are being widely implemented. We aim for optimal solute clearance, effective ultrafiltration to achieve normotension (while avoiding intradialytic symptoms) and maintenance of nutritional parameters all within the caveat that quality of life and autonomy are preserved. [ABSTRACT FROM AUTHOR]

Since the advent of maintenance dialysis therapy, our interpretation of what adequate dialysis really is has broadened and become more controversial. This is not only due to our changing and aging dialysis population but also to our evolving knowledge base. As nephrologists, we strive to achieve both quality and (often) quantity of life for our patients and we feel reassured when we have a quantifiable marker to show for our efforts. However, we suggest that adequate dialysis reaches far beyond the realms of attaining a particular biochemical result. Dialysis adequacy should encompass a more comprehensive assessment of patient well-being. This metric could comprise quality of life and patient-specified goals, sufficient small solute and middle molecule clearance, optimal blood pressure control, and effective bone-mineral balance, all in the context of minimizing mortality and morbidity, and a livable dialysis regimen for the patient. [ABSTRACT FROM AUTHOR]

Objective: This study was conducted to determine the utility of tubular (urinary/plasma neutrophil gelatinase-associated lipocalin [NGAL] and urinary kidney injury molecule 1 [KIM-1]) and glomerular (estimated glomerular filtration rate [eGFR]) biomarkers in predicting preeclampsia (PE) in pregnant women with type 1 diabetes mellitus (T1DM) who were free of microalbuminuria and hypertension at the first trimester.Research Design and Methods: This was a prospective study of T1DM pregnancy. Maternal urinary and plasma NGAL, urinary KIM-1 (ELISA of frozen samples), and eGFR (Chronic Kidney Disease Epidemiology Collaboration equation) were determined at three study visits (V1: 12.4 ± 1.8; V2: 21.7 ± 1.4; V3: 31.4 ± 1.5 weeks' gestation [mean ± SD]) in 23 women with T1DM with subsequent PE (DM+PE+), 24 who remained normotensive (DM+PE-), and, for reference, in 19 normotensive pregnant women without diabetes (DM-). The groups with diabetes were matched for age, diabetes duration, and parity. All subjects were normotensive and free of microalbuminuria or albuminuria at V1. All study visits preceded the onset of PE.Results: Urinary creatinine-corrected NGAL (uNGALcc, ng/mg) was significantly elevated at V1 in DM+PE+ vs. DM+PE- women (P = 0.01); this remained significant after exclusion of leukocyte-positive samples (5 DM+PE+ and 2 DM+PE-) (P = 0.02). Accounting for BMI, HbA1c, and total daily insulin dose, a doubling of uNGALcc at V1 conferred a sevenfold increase in risk for PE (P = 0.026). In contrast, neither plasma NGAL nor urinary KIM-1 predicted PE. Also at V1, eGFR was elevated in DM+PE+ vs. DM+PE- (P = 0.04).Conclusions: Early tubular and glomerular dysfunction may predict PE in first trimester women with T1DM, even if free of microalbuminuria. These data suggest that subclinical renal tubular and glomerular injury, if present early in pregnancy, may predispose women with T1DM to PE. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare IVIM values in pediatric renal transplants with histopathology and clinical management change. Fifteen pediatric renal transplant recipients (mean 15.7±2.9 years) were prospectively scanned on a 3T MR scanner with multi-b DTI, prior to same-day transplant biopsy. IVIM maps from 14 subjects were analyzed (one excluded due to motion). Mean values were computed from cortical ROIs and medullary ROIs corresponding to the biopsy site. Subjects were also grouped according to whether or not the biopsy resulted in a change in clinical management. Cortico-medullary IVIM estimates and histopathologic Banff scores were correlated with KT. Cortico-medullary IVIM differences between the 'change' and 'no change' groups was compared with Mann-Whitney U test. Cortical Dp showed significant moderate negative correlation with Banff t and ci scores ( KT=−0.497, P=.035 and KT=−0.46, P=.046) and moderate positive correlation with Banff i score ( KT=0.527, P=.028). Cortical P f showed significant moderate correlation with ci and ct scores ( KT=0.489, P=.035 and KT=0.457, P=.043). Tissue diffusivity, D t, estimated with IVIM was significantly different between the 'change' and 'no change' groups in medullary ROIs (U=6, P=.021). IVIM analysis has potential as a noninvasive biomarker in assessment of pediatric renal allograft pathology. [ABSTRACT FROM AUTHOR]

This communication reports invasive amoebic colitis and late onset amoebic liver abscess in three members of a group of 12 Australian travellers to Timor-Leste (TL). This is the first report of Entamoeba histolytica infection from TL. Clinicians in Australia need to consider amoebiasis in the differential diagnosis in travellers returning with colitis, abdominal pain and fever. Presentation with amoebic liver abscess months after exposure is rare but should be suspected in symptomatic individuals with a relevant history of travel. [ABSTRACT FROM AUTHOR]

There is increasing evidence that iron deposition occurs in specific regions of the brain in normal aging and neurodegenerative disorders such as Parkinson's, Huntington's, and Alzheimer's disease. Iron deposition changes the magnetic susceptibility of tissue, which alters the MR signal phase, and allows estimation of susceptibility differences using quantitative susceptibility mapping (QSM). We present a method for quantifying susceptibility by inversion of a perturbation model, or “QSIP.” The perturbation model relates phase to susceptibility using a kernel calculated in the spatial domain, in contrast to previous Fourier-based techniques. A tissue/air susceptibility atlas is used to estimate B0 inhomogeneity. QSIP estimates in young and elderly subjects are compared to postmortem iron estimates, maps of the Field-Dependent Relaxation Rate Increase, and the L1-QSM method. Results for both groups showed excellent agreement with published postmortem data and in vivo FDRI: statistically significant Spearman correlations ranging from Rho=0.905 to Rho=1.00 were obtained. QSIP also showed improvement over FDRI and L1-QSM: reduced variance in susceptibility estimates and statistically significant group differences were detected in striatal and brainstem nuclei, consistent with age-dependent iron accumulation in these regions. [ABSTRACT FROM AUTHOR]

Abstract: Structural abnormalities in temporal lobe, including the superior temporal gyrus (STG) and planum temporale (PT), have been reported in schizophrenia (SCZ) and bipolar disorder (BPD) patients. While most MRI studies have suggested gray matter volume and surface area reduction in temporal lobe regions, few have explored changes in laminar thickness in PT and STG in SCZ and BPD. ROI subvolumes of the STG from 94 subjects were used to yield gray matter volume, gray/white surface area and laminar thickness for STG and PT cortical regions. Morphometric analysis suggests that there may be gender and laterality effects on the size and shape of the PT in BPD (n =36) and SCZ (n =31) with reduced laterality in PT in subjects with SCZ but not in BPD. In addition, PT surface area was seen to be larger in males, and asymmetry in PT surface area was larger in BPD. Subjects with SCZ had reduced thickness and smaller asymmetry in PT volume. Thus, the PT probably plays a more sensitive role than the STG in structural abnormalities seen in SCZ. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Summary 1. Spatial management of marine ecosystems requires detailed knowledge of spatio-temporal mechanisms linking physical and biological processes. Tidal currents, the main driver of ecosystem dynamics in temperate coastal ecosystems, influence predator foraging ecology by affecting prey distribution and ecology. The mechanistic links between tidal currents and how they influence predator-prey behaviour and interactions at a fine scale are poorly understood. 2. Studies of fine-scale changes in oceanography, prey and predator behaviour with tidal currents require repeated surveys of the same location over brief time-scales. Such data are highly temporally and spatially autocorrelated and require appropriate analytical tools. 3. We used functional data analysis (FDA), specifically functional principal component analysis (FPCA), to analyse repeated, fine-scale, survey data collected in the North Sea. FPCA was used to explore the relationship between the behaviour of an important North Sea prey species (sandeel Ammodytes spp.) and a vulnerable surface-foraging predator (black-legged kittiwake Rissa tridactyla) with fine-scale tidally driven changes in bio-physical characteristics (temperature stratification and maximum subsurface chlorophyll concentration). 4. The FPCA indicated that sandeels were aggregated close to the surface at maximum ebb (ME) currents. Surface-feeding kittiwakes were also found in highest numbers during ME in locations of both high subsurface chlorophyll concentration and shallow sandeel aggregations. We suggest that the combination of a well-stratified water column with the movement of tidal currents over uneven topography results in surface aggregations of sandeels which kittiwakes exploit. 5. Synthesis and applications. Functional Data Analysis provides a useful tool for examining spatio-temporal patterns in natural ecosystems. In combination with fine-scale repeated survey design, we identified the importance of tide in driving prey behaviour and hence predator foraging behaviour. This has implications both for critical marine habitat identification for Marine Protected Area selection and for fisheries stock assessments. We therefore recommend that tidal aspects should be taken into account when designing marine surveys in temperate coastal ecosystems both to ensure the best identification of critical marine habitat and to improve the accuracy of fish stock assessments. [ABSTRACT FROM AUTHOR]

Objective, Design, Setting and Participants: The objective was to investigate media influence on consumers' health related behaviours. A cross-sectional survey of randomly selected adults (18+ years) residing in the Hunter Region of New South Wales Australia was conducted. The sample was selected using a combination of the white pages and random digit dialling. Main Outcome Measures: The proportions of respondents who recalled seeing or hearing about conditions or treatments in the media over the 12 months prior to interview (August 2009-August 2010) and their subsequent health related behaviour. Results: Although most survey participants reported seeking health information from their doctors, around two-thirds of survey participants (551, 68.8%) recalled hearing, seeing or reading about one or more medical conditions (total = 1097 instances) in the mainstream media over the past 12 months. Almost 40% of respondents (307, 38.4%) stated that they had looked for more information about a condition as a result of hearing about it in the media, and most used the internet (269, 87.4%). More than a quarter of respondents (215, 26.9%) indicated that they had asked their doctor about a condition they had heard about in the media. Around half of those who asked their doctor (109, 50.6%) reported that their inquiry resulted in them receiving treatment, of whom almost half (53, 48.3%) reported being prescribed a medicine. Conclusion: The survey results show that consumers become aware of medicines through traditional media and then to learn more often turn to the internet where quality of information may be poor. (252 words) [ABSTRACT FROM AUTHOR]

"Learning through Art" was a project that emerged from the OLLI @Berkeley "Learning to Learn" Interest Circle in the summer of 2009. More than 30 Interest Circle members explored their own learning styles and strengths, and explored the newest research in neuroscience and aging in order to seek ways of applying that science to their own everyday lives. [ABSTRACT FROM AUTHOR]

Abstract: The harbour porpoise is a highly mobile species and thus represents a considerable challenge in the context of using marine protected areas (MPAs) for conservation. The shelf waters off the west coast of Scotland have been identified as an area of year-round presence, high density in comparison to surrounding areas, and a high young to adult ratio in summer and are thus a suitable area for exploring the location of possible special areas of conservations (SACs) under the EU Habitats Directive. We carried out dedicated surveys over three summers in the southern Inner Hebrides and used generalised additive models (GAMs) to predict areas of high relative density for harbour porpoises for each year. After compensating for survey effects, static bathymetric and persistent hydrographic variables were used in a step-wise model selection procedure. In all years harbour porpoise distribution was best explained by maximum tidal current, with higher densities predicted in areas of low current, and the same high density areas predicted year-on-year. Perimeter-to-area ratio was used to identify which areas should be considered as a basis for designating SACs for harbour porpoise in this area, to form part of the Natura 2000 network. The method used here combines spatial modelling and perimeter-to-area ratio for selecting protected areas, a methodology which is suitable for the protection of other animal species. [Copyright &y& Elsevier]

Abstract: Functional neuroimaging studies of endogenous cued attention suggest that a fronto-parietal attentional network keeps track of current task objectives in working memory and enhances activity in posterior sensory regions that underlie the perceptual processing of behaviorally relevant stimuli. Relatively little is known, however, about whether consciously perceived, irrelevant instructional cues can hijack the attentional network, leading to an enhancement of the perceptual processing of irrelevant stimuli. Using a cross-modal attentional cueing task in combination with functional magnetic resonance imaging, we found that such irrelevant cues can indeed hijack the attentional network, as indexed by increased activity in (a) frontal regions that control attention and (b) sensory cortices that underlie the perceptual processing of task-irrelevant stimuli. Furthermore, we found that in left ventrolateral (but not dorsolateral) prefrontal regions, the magnitude of this increased activity varies with whether an irrelevant instructional cue is presented simultaneously with (versus after) a relevant instructional cue. These findings show that consciously perceived, irrelevant instructional cues can activate inappropriate task objectives in working memory, resulting in a hijacking of the attentional network. Moreover, they reveal different time courses of hijacking effects in ventrolateral and dorsolateral prefrontal regions, consistent with models in which these regions make distinct contributions to cognitive control. [Copyright &y& Elsevier]

The debate over genetically modified foods has become one of the defining environmental and social issues of the past decade. As the public naturalize biotechnology within existing cultural systems, this produces what I term ‘cultures of GM’. This paper examines how these ‘cultures’ are legitimized and sustained through an appraisal of divergent North American and European conceptions of risk and their translation into food labelling policies. It is argued that the dialectical relationship between risk perception and its cultural context offers an instructive vantage point for critical reflection by geographers. [ABSTRACT FROM AUTHOR]

Triiodothyronine (T3) classically regulates gene expression by binding to high-affinity thyroid hormone receptors (TR) that recognize specific response elements in the promoters of T3-target genes and activate or repress transcription in response to hormone. However, a number of thyroid hormone effects occur rapidly and are unaffected by inhibitors of transcription and translation, suggesting that thyroid hormones may also mediate non-genomic actions. Such actions have been described in many tissues and cell types, including brown adipose tissue, the heart and pituitary. The site of non-genomic hormone action has been localized to the plasma membrane, cytoplasm and cellular organelles. These non-genomic actions include the regulation of ion channels, oxidative phosphorylation and mitochondrial gene transcription and involve the generation of intracellular secondary messengers and induction of [Ca2+]I, cyclic AMP or protein kinase signalling cascades. These observations have been interpreted to imply the presence of a specific, membrane associated, TR isoform or an unrelated high affinity membrane receptor for thyroid hormone. The recent identification of a progestin membrane receptor and the sub cellular targeted nuclear receptor isoforms ER46, mtRXR, mtPPAR, p28 and p46, has highlighted the potential importance of non-genomic actions of steroid hormones. Here we compare these recently identified receptors with the genomic, non-genomic and mitochondrial actions of thyroid hormones and consider their implications. [Copyright &y& Elsevier]

Diagnosis of neurological conversion disorder is difficult. Considerable overlap in symptomatology occurs with progressive neurological degenerative disease, pervasive refusal syndrome, depressive illness, chronic fatigue syndrome, and other conditions. Conversion symptoms can also coincide with organic neurological disease. Successful management requires a sensitive, confident, multidisciplinary approach. Multiple or repeated investigations can be counterproductive in resolving symptoms. This report describes three children, one male and two female, aged between 9 and 10 years, who were referred for evaluation of progressive neurological symptoms. Each progressed to a completely dependent state within 8 weeks of referral, requiring nasogastric feeding and total assisted care. A convincing psychosocial trigger was not identified in any case. Improvement occurred only when investigations were ceased and rehabilitation commenced. Long-term follow-up has revealed an excellent outcome for all three children. [ABSTRACT FROM AUTHOR]

Twelve commercial clones of poplar were cultured in vitro from meristem tips (0.3–0.5 mm diameter), shoot tips (4–6 mm long) and nodal segments (5–10 mm long). Shoot‐producing cultures were obtained from 4, 32 and 70% of meristem tips, shoot tips and nodal segments within 12, 6 and 4 weeks, respectively. The genotype of cultures had a greater influence on development of shoot‐producing cultures than medium composition. Cultivars Max/Ber and Oxford had the highest rates of establishment in culture and subsequent shoot proliferation, while P. tacamahaca, P. trichocarpa and cv. Robusta exhibited very low rates of establishment and low vigor in vitro. Shoot tip development was best on agar‐solidified medium whereas liquid medium resulted in vitrification. Higher rates of axillary shoot production from established cultures were obtained with benzyladenine or zeatin than with 2‐isopentenyladenine. Reducting the benzyladenine concentration from 4.4 to 1.1 μM, increased the production of elongated shoots suitable for rooting. [ABSTRACT FROM AUTHOR]

Under controlled environmental conditions, inoculation of barley at five growth stages with Rhynchosporium secalis reduced grain yield by up to 30%. Greater yield losses resulted from inoculations carried out after tillering than from those during or before tillering. Most of the yield loss was due to a reduction in the number of heads per plant. The number of grains per head was reduced only when plants were inoculated at mid- or late-tillering growth stages. The mean weight of individual grains was not reduced significantly by any treatment. Inoculation at stem elongation also resulted in less leaf area and water use, and delayed anthesis. Inoculation affected root dry weight more than shoot dry weight and all inoculations reduced root dry weight at the boot growth stage. [ABSTRACT FROM AUTHOR]

Sediment cores were collected from two lakes in the Courageous Lake Greenstone Belt (CLGB), central Northwest Territories, Canada, to examine the influence of late-Holocene warming on the transport and fate of arsenic (As) in sub-Arctic lakes. In both lakes, allochthonous As-bearing minerals (i.e. arsenopyrite and scorodite) were identified in sediment deposited during times of both regional warming and cooling, suggesting that weathering of bedrock and derived surficial materials provides a continual source of As to lakes of the CLGB. However, maximum porewater As (84 μg·L−1 and 15 μg·L−1) and reactive organic matter (OM; aquatic and terrestrial-derived) concentrations in each lake are coincident with known periods of regional climate warming. It is inferred that increased biological production in surface waters and influx of terrigenous OM led to the release of sedimentary As to porewater through reductive dissolution of As-bearing Fe-(oxy)hydroxides and scorodite during episodes of regional warming. Elevated sedimentary As concentrations (median: 36 mg·kg−1; range: 29 to 49 mg·kg−1) are observed in sediment coeval with the Holocene Thermal Maximum (ca. 5430 ± 110 to 4070 ± 130 cal. years BP); at these depths, authigenic As-bearing framboidal pyrite is the primary host of As in sediment and the influence of organic matter on the precipitation of As-bearing framboidal pyrite is apparent petrographically. These findings suggest that increased biological productivity and weathering of terrestrial OM associated with climate warming influences redox cycles in the near-surface sediment and enhances the mobility of As in northern lakes. Knowledge generated from this study is relevant for predicting future climate change-driven variations in metal(loid) cycling in aquatic systems and can be used to interpret trends in long-term environmental monitoring data at historical, modern, and future metal mines in northern environments. Unlabelled Image • Late-Holocene warming increased the mobility of As in sub-Arctic lake sediments. • Catchment weathering provides a continuous natural source of As to lakes. • Labile organic matter plays a key role in sequestering As in lake sediments. • Organic matter increases due to regional warming and enhances the mobility of As. • Climate warming will influence the long-term mobility of As in northern lakes. [ABSTRACT FROM AUTHOR]

The article presents a response on the comment of the study regarding the association of sublicnical first trimester renal abnormalities with preeclampsia (PE) in women in pregnant women with type 1 diabetes. It highlights several important issues in the comment and recognizes the need for a confirmatory study before translating the findings into clinical use. The authors also argue that they provide important clues to the underlying reasons for susceptibility to PE in women with diabetes.

Climate change is influencing the biogeochemistry of northern lake ecosystems. These changes may affect the mobility of naturally occurring metal(loid)s and long-term stability of anthropogenic contaminants. Arsenic (As) concentrations in lake sediments in the Courageous Lake Greenstone Belt, Northwest Territories, Canada, are elevated from the operation of two high-grade, low-tonnage historical gold mines (Tundra Mine and Salmita Mine) and the weathering of mineralized bedrock. In sensitive sub-Arctic environments, it is not currently known how the cumulative effects of resource extraction and climate warming will impact geochemical baselines and the long-term stability of legacy contaminants. In this study, measurements of As concentration and speciation in waters and sediments are combined with multivariate analyses of climate proxies (sediment particle size and organic matter composition) from five lakes downstream of the former Tundra Mine site. Data from lake sediment cores were divided into geochemically distinct populations using a combination of radiometric dating and constrained incremental sum-of-squares cluster analysis to define geochemical baselines, examine the lake-specific controls on As distribution, and determine climate-related factors that may influence the long-term stability of As. Median As concentrations in near-surface impacted sediments (median: 110 mg kg−1; range: 31–1,010 mg kg−1; n = 22) and pre-mining sediment (median: 40 mg kg−1; range: 28–170 mg kg−1; n = 102) exceed the Canadian Council of the Ministers of the Environment Probable Effects Level of 17 mg kg−1. Near the Tundra Mine, the long-term stability of As in the near-surface sediment is influenced by the source of As (direct disposal and weathering of waste rock, tailings overtopping and seepage, discharge of treated tailings effluent, weathering and airborne deposition of tailings and waste rock, and natural weathering of mineralized bedrock), lithology of the sediment, and composition of sediment organic matter. This study demonstrates that in lakes impacted by weathering of waste rock and mineralized bedrock, As in sediments is primarily hosted by Fe-(oxy)hydroxides and may be more susceptible to remobilization with climate warming relative to those lakes impacted by direct discharge of mine wastes where As-bearing sulphides are the most abundant As host. Continued climate warming is expected to increase the natural loading of metal(loid)s and organic matter to lake sediments; however, the effects of these changes on the long-term stability of legacy contaminants will vary between lakes. Image 1 • Climate warming will influence the long-term stability of arsenic in northern lakes. • The stability of arsenic in sediments depends on its source and solid-phase speciation. • Geochemical baselines vary between lakes in sub-Arctic, mineralized environments. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE), a major cause of maternal and fetal morbidity and mortality worldwide, has significantly higher incidence in women with type 1 diabetes mellitus (T1DM) than in nondiabetic populations (∼20% vs. 5%, respectively). Sphingolipids are key signaling molecules, and have many roles in the structure and regulation of cellular functions. Sphingomyelin (SM) is the most abundant sphingolipid in plasma lipoproteins. There is evidence that altered SM metabolism may contribute to cardiovascular and renal complications in diabetes. We aimed to determine whether plasma concentrations of 12 SM species were associated with PE in T1DM in a prospective study of pregnancy of 23 T1DM women who developed PE and 24 T1DM who remained normotensive. Additionally, 19 normotensive nondiabetic pregnant women were included for reference. All subjects were free of microalbuminuria and hypertension at enrolment, and all visits (12, 22, 32 weeks' gestation) preceded clinical PE onset. Results: There were no cross-sectional differences in total SM, or in any individual SM species, between diabetic women with and without PE, or between normotensive women with and without diabetes at any stage of gestation. With advancing gestation in all groups, C18-SM, C18:1-SM, C20-SM, C20:1-SM, C22-SM, C22:1-SM, C24-SM, and C24:1-SM increased (all p<0.001). LDL- and VLDL-cholesterol also increased, while HDL-cholesterol did not change. In contrast, C14-SM, C16-SM, C26-SM and C26:1-SM decreased (all p<0.001). There were no correlations between any SM species and conventional lipid profiles. Conclusions: With advancing gestation, plasma concentrations of most SM species increased, as did LDL and VLDL; however, two long-chain and two very long-chain SM species decreased. Although there were no differences in SM according to diabetes or PE status at any time point, further studies should address the significance of differential changes of SM species during pregnancy. Disclosure: C.B. Kelly: None. S.M. Hammad: None. R.L. Klein: None. M.F. Lopes-Virella: None. M.J. Leyva: None. J. Yu: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.J. Nankervis: None. K.F. Hanssen: None. S.K. Garg: Advisory Panel; Self; Eli Lilly and Company, Roche Pharma, Sanofi-Aventis, Zealand Pharma A/S. Research Support; Self; Eli Lilly and Company, WebMD. J.A. Scardo: None. C.E. Aston: None. T. Lyons: None. Funding: JDRF; Novo Nordisk; National Institutes of Health [ABSTRACT FROM AUTHOR]

The risk for preeclampsia (PE) is increased 4-fold in women with type 1 diabetes (T1D), in whom we previously demonstrated that elevated cholesterol-rich lipoproteins confer risk at the 1st trimester. Sphingolipids, including ceramides (Cer) and glycosphingolipids (hexosyl- (HexCer) and lactosyl-ceramides (LacCer)), are lipoprotein constituents that regulate cell signaling. We propose that these bio-active lipids could be modulators of PE risk. In a prospective T1D pregnancy cohort (studied at 12, 22, 32 weeks' gestation), we used liquid chromatography/electrospray ionization-tandem mass spectrometry to determine plasma levels of 12 species of Cer, HexCer, and LacCer in 23 women with T1DM who did vs. 24 who did not develop PE, and in 19 normotensive nondiabetic pregnant women. All were free of microalbuminuria and hypertension at enrolment; all visits preceded clinical PE onset. Results: Plasma levels of C22-Cer (1st and 3rd study visits); C26:1-Cer (1st and 2nd visits); C26-Cer (1st visit); C18-Cer and C18:1-Cer (2nd visit) were significantly higher in women with T1DM who did vs. did not develop PE. C22-Cer and C26-Cer were significantly lower in T1DM vs. non-T1DM (1st visit). There were no overall PE- or diabetes-related differences in any HexCer- or LacCer species. Longitudinally, most Cer and HexCer species increased throughout pregnancy in all groups (except C14- and C18-Cer; and C14 and C26-HexCer). C16-LacCer increased, while C22:1-, C26-, and C26:1-LacCer decreased as pregnancy advanced, independent of PE status. Independent of LDL-C, total Cer increased throughout pregnancy in all groups. Conclusions: Maternal Cer species may serve as early biomarkers for PE in women with T1DM. T1DM was associated with lower levels of two Cer species. Like cholesterol-rich lipoproteins, Cer, HexCer and some LacCer species increase as pregnancy advances in all groups, but other LacCer species decrease: the significance of these findings requires further study. Disclosure: C.B. Kelly: None. S.M. Hammad: None. R.L. Klein: None. M.F. Lopes-Virella: None. M.J. Leyva: None. J. Yu: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.J. Nankervis: None. K.F. Hanssen: None. S.K. Garg: Advisory Panel; Self; Eli Lilly and Company, Roche Pharma, Sanofi-Aventis, Zealand Pharma A/S. Research Support; Self; Eli Lilly and Company, WebMD. J.A. Scardo: None. C.E. Aston: None. T. Lyons: None. Funding: JDRF; Novo Nordisk; National Institutes of Health [ABSTRACT FROM AUTHOR]

Statin therapy reduces cardiovascular risk in type 2 diabetes (T2DM), partly by improving dyslipidemia, and partly through 'pleiotropic' effects. Sphingolipids, including ceramides, are amphiphilic components of lipoprotein surface monolayers. Sphingolipids regulate lipoprotein surface fluidity, and include key signaling molecules: ceramides are specifically associated with apoptosis and risk for premature coronary heart disease. Effects of statins on the sphingolipid content of lipoproteins are poorly defined. Using liquid chromatography/electrospray ionization-tandem mass spectrometry, we determined fasting plasma concentrations of individual ceramides (Cer), sphingomyelins (SM), and glycosphingolipids (hexosyl- and lactosyl-Cer) in plasma from 19 men and 21 women with T2DM, before and after treatment with rosuvastatin (10 mg/day, 6 weeks). Exclusion criteria were use of 'statins' in the preceding 6 months, and any current use of lipid-modifying agents. Using existing lipoprotein compositional data, we calculated effects of rosuvastatin therapy on non-HDL sphingolipid content. Results: Rosuvastatin reduced total cholesterol (C) (by 33%), triglycerides (20%), LDL-C (49%), and non-HDL particle number (34%); HDL-C was unaffected. It decreased total SM (15%), Cer (29%), and hexosyl- (30%) and lactosyl- (34%) Cer, independent of gender. Assuming HDL composition was unaffected, rosuvastatin reduced non-HDL SM by 42% and Cer by 61%: these reductions remained significant after correction for non-HDL-C and/or non-HDL lipoprotein surface area. Conclusions: In T2DM, rosuvastatin lowers not only the number of non-HDL particles, but also the sphingolipid, and especially the Cer, content of each particle. This effect is independent of gender, potentially anti-atherogenic, and may represent a new pleiotropic effect of statins. Further studies are needed to confirm these findings in isolated lipoprotein classes, and to determine mechanism(s). Disclosure: C.B. Kelly: None. S.M. Hammad: None. R.L. Klein: None. M.F. Lopes-Virella: None. A. Gosmanova: None. M.J. Leyva: None. C.E. Aston: None. T. Lyons: None. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) occurs four times more frequently in pregnant women with type 1 diabetes (T1D) than in nondiabetic women. We hypothesized that elevated plasma advanced glycoxidation products (AGEs) predict PE in T1D women. In a prospective T1D pregnancy cohort (study visits at 12, 22, 32 weeks' gestation), we used liquid chromatography/mass spectrometry, with internal stable heavy isotope substituted standards, to determine plasma levels of nine AGE and oxidation products (carboxymethyl-lysine [CML], carboxyethyl-lysine [CEL], methylglyoxal-hydroimidazolone [MGHI], 3-deoxyglucosone hydroimidazolones [3DGH], methionine sulfoxide [MetSO], glyoxal hydroimidazolone [GHI], 3-nitrotyrosine [3NT], dityrosine [DT], 2-aminoadipic acid [2AAA]) in 23 women with T1DM who developed PE vs. 24 who did not, and in 19 nondiabetic normotensive pregnant women. These products have been associated with CVD and renal failure in non-pregnant cohorts. All women were free of microalbuminuria and hypertension at enrolment, and all visits preceded clinical PE onset. GFR was estimated (Chronic Kidney Disease Epidemiology Collaboration equation). Results: Plasma CML, CEL, MGHI, 3DGH, MetSO, GHI, and 2AAA did not differ between the three groups at any study visit, and thus did not predict preeclampsia in T1D. In T1D women who later developed PE, eGFR was inversely associated at V3 with CML (p=0.008), CEL (p=0.03), MGH1 (p=0.03), 3DGH (p=0.03), GHI (p<0.001), and 2AAA (p<0.05); and at V2 with CEL (p=0.04), MGHI (p=0.02), and GHI (p=0.02). No such associations were observed in normotensive T1D or in nondiabetic pregnant women. Plasma levels of 3NT and DT were undetectable in all participants. Conclusions: Plasma AGEs did not predict PE in well-controlled, previously healthy T1D women, and levels did not differ from healthy nondiabetic controls. Uniquely, in T1D women who developed PE, plasma AGEs were associated with renal function, consistent with the notion that subclinical alterations in renal function precede PE. Disclosure: H. Karanchi: None. C.B. Kelly: None. S.M. Hammad: None. R.L. Klein: None. M.F. Lopes-Virella: None. M.J. Leyva: None. J. Yu: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.J. Nankervis: None. K.F. Hanssen: None. C.E. Aston: None. S. Howell: Employee; Self; PreventAGE Health Care, LLC. P.J. Beisswenger: Other Relationship; Self; PreventAGE Health Care, LLC. T. Lyons: None. [ABSTRACT FROM AUTHOR]

Rapid development of a successful foraging strategy is critical for juvenile survival, especially for naïve animals that receive no parental guidance. However, this process is poorly understood for many species. Although observation of early‐life movements is increasingly possible with miniaturisation of animal‐borne telemetry devices, analytical limitations remain. Here, we tracked 29 recently‐weaned grey seal Halichoerus grypus pups from colonies in two geographically distinct regions of the United Kingdom. We analysed at‐sea movements of pups throughout their initial months of nutritional independence to investigate the ontogeny of behaviour‐specific (foraging and travelling) movement patterns. Using generalized hidden Markov models (HMMs), we extended the conventional HMM framework to account for temporal changes in putative foraging and travelling movement characteristics, and investigate the effects of intrinsic (sex) and extrinsic (environment) factors on this process. Putative foraging behaviour became more tortuous with time, and travelling became faster and more directed, suggesting a reduction in search scale and an increase in travel efficiency as pups shifted from exploration to an adult‐like repeatable foraging strategy. Sex differences in movement characteristics were evident from colony departure, but sex‐specific activity budgets were only detected in one region. We show that sex‐specific behavioural strategies emerge before sexual size dimorphism in grey seals, and suggest that this phenomenon may occur in other long‐lived species. Our results also indicate that environmental variation may affect the emergence of sex‐specific foraging behaviour, highlighting the need to consider interacting intrinsic and extrinsic factors in shaping movement strategies of long‐lived vertebrates. Moreover, comparing the behavioural state estimations to those of a conventional HMM (no variation in state‐specific movement parameters) revealed differences in the amount and location of foraging activity, with implications for spatial conservation management. Overlooking intrinsic and extrinsic variation in movement processes could distort our understanding of foraging ecology, population dynamics and conservation requirements. [ABSTRACT FROM AUTHOR]

During the twentieth century, inadequate management of mine waste at the Mount Lyell Copper Mine affected the ecology of the Queen–King Rivers and Macquarie Harbour, western Tasmania, Australia. Over the past two decades, the water quality of the river system has been measured semi-annually to investigate the long-term hydrochemical and environmental impacts caused by these historical mine practices and the waste associated with the Mount Lyell mine to the Queen–King Rivers. At sample sites below the confluence of Haulage Creek, the water pH was below pH 3.5, remaining below pH 5 across all sites to Macquarie Harbour. Local baseline rivers ranged from pH 4.0 to 8.4. Elemental concentrations of dissolved metals in water samples downstream of Haulage Creek were above the Australian and New Zealand Environment and Conservation Council (ANZECC) water quality guidelines. Copper, Fe, and Zn were not attenuated along the length of the river, with concentrations remaining elevated to the King River Delta. Mineralogical analyses demonstrated secondary minerals in sediments at Haulage Creek and pyrite concentrated at the King River Delta. Static tests on mining-affected sediments indicated risk of AMD and metal(loid) leaching in the river system. Since 2016, after flooding of the Prince Lyell mine, dissolved metal levels in the Queen–King Rivers have decreased; however, concentrations remain above guidelines. Almost three decades after legacy mine waste disposal ended, it still poses a long-term risk to the downstream environment, implying that without effective management of these historical mine wastes, the Queen–King Rivers will continue to be severely impacted. [ABSTRACT FROM AUTHOR]

Transcription factors represent a major mechanism by which cells establish basal and conditional expression of proteins, the latter potentially being adaptive or maladaptive in disease. The complement of transcription factors in two major structural cells of the lung relevant to asthma, airway epithelial and smooth muscle cells, is not known. A plate-based platform using nuclear extracts from these cells was used to assess potential expression by binding to oligonucleotide consensus sequences representing >300 transcription factors. Four conditions were studied: basal, β-agonist exposure, culture under proasthmatic conditions (IL- 13, lL-4, TGF-β, and leukotriene D4), and the dual setting of β-agonist with proasthmatic culture. Airway epithelial cells expressed 70 transcription factors, whereas airway smooth muscle expressed 110. High levels of multiple transcription factors not previously recognized as being expressed in these cells were identified. Moreover, expression! binding patterns under these conditions revealed extreme discordance in the direction and magnitude of change between the cell types. Singular (one cell type displayed regulation) and antithetic (both cell types underwent expression changes but in opposite directions) regulation dominated these patterns, with concomitant regulation in both cell types being rare (<10%). β-Agonist evoked up- and downregulation of transcription factors, which was highly influenced by the proasthmatic condition, with little overlap of factors regulated by β-agonists under both conditions. Together, these results reveal complex, cell type-dependent networks of transcription factors in human airway epithelium and smooth muscle that are dynamically regulated in unique ways by β-agonists and inflammation. These factors may represent additional components in asthma pathophysiology or potential new drug targets. [ABSTRACT FROM AUTHOR]

Objective: We assessed the safety of long-term varenicline administration for smoking cessation.Methods: In this randomized, double-blind, multicenter trial, eligible adult smokers (18–75 years) who smoked an average of ≥10 cigarettes/day were randomized to either varenicline 1 mg twice daily (BID) or placebo for 52 weeks. Subjects made weekly clinic visits until week 8, and then every 4 weeks until week 52, with a follow-up visit at week 53. The target quit date was the morning of the week 1 clinic visit. Brief counseling was provided at each visit, and vital signs, adverse events (AEs), and smoking status were documented. Other laboratory measures were collected at specified visits.Results: A total of 251 subjects were randomized to varenicline and 126 to placebo. Approximately half of the subjects in each arm completed the study (53.8% varenicline; 46.8% placebo). Treatment-emergent AEs were observed in 96.4% of varenicline- and 82.5% of placebo-treated subjects during the study. Common varenicline-associated AEs were nausea (40.2%), abnormal dreams (22.7%), and insomnia (19.1%). Most AEs were considered mild or moderate in intensity. AEs leading to discontinuation of varenicline treatment included nausea (7.6%), insomnia (3.2%), and abnormal dreams (2.4%). A single varenicline-related serious AE, bilateral subcapsular cataracts, was observed. At week 52, 7-day point prevalence abstinence rates were 36.7% (varenicline) and 7.9% (placebo).Conclusions: Varenicline 1 mg BID can be safely administered for up to 1 year. Varenicline was also a more effective smoking cessation aid than placebo throughout the study, supporting both its short- (12-week) and long-term (52-week) efficacy. [ABSTRACT FROM AUTHOR]

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 < 0.001) from ADG discretionary items were lower in personalised nutrition vs control. There were greater reductions in ADG percentage energy and percentage total fat, SFA and salt for those randomised to L3 vs L2. Conclusions: Compared with generalised dietary advice, personalised nutrition advice achieved greater reductions in discretionary foods intake when the classification included all foods high in fat, added sugars and salt. Future personalised nutrition approaches may be used to target intake of discretionary foods. Trial registration: Clinicaltrials.gov NCT01530139. Registered 9 February 2012. [ABSTRACT FROM AUTHOR]

Purpose: Prolonged nearwork has been implicated in myopia progression. Accommodation responses of young‐adult myopes wearing different multifocal contact lenses were compared. Methods: Twenty adults, 18–25 years, with myopia (spherical equivalent refraction −0.50 to −5.50 D, mean −2.1 ± 1.6 D) wore five lens types in random order: Proclear single vision distance (SV), MiSight concentric dual‐focus +2.00 D Add (MS), Biofinity aspheric centre distance +1.50 D Add (CD1) and +2.50 D Add (CD2) (all Coopervision), and NaturalVue aspheric (Visioneering Technologies) (NVue). Using a Grand‐Seiko WAN‐5500 autorefractor with binocular correction and viewing right eye accommodative responses were measured after a 10 min adaptation period at 4.0, 1.0, 0.5, 0.33 and 0.25 m distances. Dynamic measurements were taken for 4 s at 6 Hz. Accommodative stimuli and responses were referenced to 4 m (i.e., refraction differences between 4 m and nearer distances). Accommodation lags and refraction instabilities (standard deviations of dynamic responses) were determined. For comparison, results were obtained for an absolute presbyopic eye, where trial lenses counteracted the accommodation stimulus. Results: For SV and MS, accommodation responses were similar to the stimulus values. For aspheric lenses CD1, CD2 and NVue, accommodation responses were approximately 1.0 D lower across the stimulus range than with SV and MS, and rates of change were approximately 0.84 D per 1 D stimulus change. MS produced greater refraction instabilities than other lenses. For the presbyope, changes in refraction matched the trial lenses, indicating that corrections due to measurement through the different lenses were not needed. Conclusion: Reductions in accommodation response occurred in young myopes wearing aspheric multifocal contact lenses independent of the labelled 'add' power. The concentric dual‐focus MS lens produced minimal lags but had greater instability than the other lenses. The results indicate that the mechanism of multifocal contact lenses slowing myopia progression is unlikely to be through relaxing accommodation, at least in young adults. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Mouse Ccr1l1 (Ccr1-like 1) encodes an orphan G-proteincoupled receptor (GPCR) with the highest homology to the inflammatory and highly promiscuous chemokine receptors Ccr1 and Ccr3 (70 and 50% amino acid identity, respectively). Ccr1l1 was first cloned in 1995, yet current knowledge of this putative chemokine receptor is limited to its gene organization and chromosomal localization. Here we report that Ccr1l1 is a Rodentia-specific gene selectively expressed in eosinophils. However, eosinophil phenotypes, development, and responsiveness to chemokines were all normal in naïve Ccr1l1 knockout mice. We demonstrate for the first time that recombinant Ccr1l1 is expressed on the plasma membrane of transfected cells and contains an extracellular N terminus and an intracellular C terminus, consistent with GPCR topology. Using receptor internalization, ß-arrestin recruitment, calcium flux, and chemotaxis assays, we excluded all 37 available mouse chemokines, including Ccr1 ligands, and two viral chemokines as Ccr1l1 ligands, and demonstrated that mouse Ccr1, but not Ccr1l1, exhibits constitutive signaling activity. However, sequence analysis and structural modeling revealed that Ccr1l1 is well equipped to act as a classical signaling GPCR, with N-terminal sulfotyrosines as the only signaling and chemokinebinding determinant absent in Ccr1l1. Hereof, we show that a sulfatable N-terminal Ccr1 Y18 residue is essential for chemotaxis and calcium responses induced by Ccl3 and Ccl9/10, but substituting the corresponding Ccr1l1 F19 residue with tyrosine failed to confer responsiveness to Ccr1 ligands. Although Ccr1l1 remains an extreme outlier in the chemokine receptor family, our study supports that it might respond to unidentified mouse chemokine ligands in eosinophil-driven immune responses. [ABSTRACT FROM AUTHOR]

Given the recent trend towards establishing very large marine protected areas (MPAs) and the high potential of these to contribute to global conservation targets, we review outcomes of the last decade of marine conservation research in the British Indian Ocean Territory (BIOT), one of the largest MPAs in the world. The BIOT MPA consists of the atolls of the Chagos Archipelago, interspersed with and surrounded by deep oceanic waters. Islands around the atoll rims serve as nesting grounds for sea birds. Extensive and diverse shallow and mesophotic reef habitats provide essential habitat and feeding grounds for all marine life, and the absence of local human impacts may improve recovery after coral bleaching events. Census data have shown recent increases in the abundance of sea turtles, high numbers of nesting seabirds and high fish abundance, at least some of which is linked to the lack of recent harvesting. For example, across the archipelago the annual number of green turtle clutches (Chelonia mydas) is ~ 20,500 and increasing and the number of seabirds is ~ 1 million. Animal tracking studies have shown that some taxa breed and/or forage consistently within the MPA (e.g. some reef fishes, elasmobranchs and seabirds), suggesting the MPA has the potential to provide long-term protection. In contrast, post-nesting green turtles travel up to 4000 km to distant foraging sites, so the protected beaches in the Chagos Archipelago provide a nesting sanctuary for individuals that forage across an ocean basin and several geopolitical borders. Surveys using divers and underwater video systems show high habitat diversity and abundant marine life on all trophic levels. For example, coral cover can be as high as 40–50%. Ecological studies are shedding light on how remote ecosystems function, connect to each other and respond to climate-driven stressors compared to other locations that are more locally impacted. However, important threats to this MPA have been identified, particularly global heating events, and Illegal, Unreported and Unregulated (IUU) fishing activity, which considerably impact both reef and pelagic fishes. [ABSTRACT FROM AUTHOR]