Diffusion-based spatial priors for imaging.

We describe a Bayesian scheme to analyze images, which uses spatial priors encoded by a diffusion kernel, based on a weighted graph Laplacian. This provides a general framework to formulate a spatial model, whose parameters can be optimised. The standard practice using the software statistical parametric mapping (SPM) is to smooth imaging data using a fixed Gaussian kernel as a pre-processing step before applying a mass-univariate statistical model (e.g., a general linear model) to provide images of parameter estimates (Friston et al., 2006). This entails the strong assumption that data are generated smoothly throughout the brain. An alternative is to include smoothness in a multivariate statistical model (Penny et al., 2005). The advantage of the latter is that each parameter field is smoothed automatically, according to a measure of uncertainty, given the data. Explicit spatial priors enable formal model comparison of different prior assumptions, e.g. that data are generated from a stationary (i.e. fixed throughout the brain) or non-stationary spatial process. We describe the motivation, background material and theory used to formulate diffusion-based spatial priors for fMRI data and apply it to three different datasets, which include standard and high-resolution data. We compare mass-univariate ordinary least squares estimates of smoothed data and three Bayesian models spatially independent, stationary and non-stationary spatial models of non-smoothed data. The latter of which can be used to preserve boundaries between functionally selective regional responses of the brain, thereby increasing the spatial detail of inferences about cortical responses to experimental input

Renal pericytes: regulators of medullary blood flow

Regulation of medullary blood flow (MBF) is essential in maintaining normal kidney function. Blood flow to the medulla is supplied by the descending vasa recta (DVR), which arise from the efferent arterioles of juxtamedullary glomeruli. DVR are composed of a continuous endothelium, intercalated with smooth muscle-like cells called pericytes. Pericytes have been shown to alter the diameter of isolated and in situ DVR in response to vasoactive stimuli that are transmitted via a network of autocrine and paracrine signalling pathways. Vasoactive stimuli can be released by neighbouring tubular epithelial, endothelial, red blood cells and neuronal cells in response to changes in NaCl transport and oxygen tension. The experimentally described sensitivity of pericytes to these stimuli strongly suggests their leading role in the phenomenon of MBF autoregulation. Because the debate on autoregulation of MBF fervently continues, we discuss the evidence favouring a physiological role for pericytes in the regulation of MBF and describe their potential role in tubulo-vascular cross-talk in this region of the kidney. Our review also considers current methods used to explore pericyte activity and function in the renal medulla

The association between dietary macronutrient intake and fibrogen growth factor 21 in a sample of White UK adults with elevated cardiometabolic risk markers

Increased levels of Fibrogen growth factor 21 (FGF21) is an emerging risk marker for cardiometabolic (CM) disease(1). Little detail is known about the impact of the human diet on FGF21 levels. The aim of this investigation was to assess potential associations between mean daily dietary macronutrient intake and FGF21 levels in a sample of 10 healthy normal-weight and overweight Caucasian adults aged 32–60 (80 % male) at increased CM risk(2). This pilot study received ethical approval from Liverpool John Moores University Research Ethics Committee (16/ELS/029) and was registered with ClinicalTrials.gov (Ref. NCT03257085). Participants were randomly allocated to one of two groups and asked to either consume 50 % energy from CHO for a duration of 8 weeks. Blood plasma samples were col- lected at baseline (BL), interim point (IP) and endpoint (EP) after a 12-hour overnight fast, immediately processed and frozen at −80°C. Thawed plasma samples were analysed via Quantikine® enzyme-linked immunosorbent assay (ELISA) (R&D Systems) for FGF21 levels. Two-way mixed ANOVA and Pearson’s partial correlation adjusted for estimated weekly moderate and vigorous activity was undertaken using IBM SPSS 24®. There were no effects for diet between groups or over time (data not shown). Significant correlations between macronutrient intakes and FGF21 levels were found for both groups at IP, but not at BL or EP. Moderate and significant positive correlations were found in the overall group for intake (g/d) for glucose (rpartial = ·699, p = ·04) and fructose (rpartial = ·686, p = ·04) and strong and significant positive correlations for non-milk extrinsic sugars (rpartial = ·742, p = ·02). Strong and significant positive correlations were also found in the LC group for glucose intake (g/d) (rpartial = ·980, p = ·02) and fructose (rpartial = ·967, p = ·03) and for protein (rpartial =·998, p=·002) after adjusting for physical activity. Mean carbohydrate intake (g/d) was 160·0 (s.d. 124·5) overall and 44·2 (s.d. 14·9) in the LC group at IP. Mean protein intake (g/d) was 113·2 (21·4) 130·0 (s.d. 15·9) overall and in the LC group at IP. Mean FGF21 levels were 179·9 pg/mL (s.d. 144·9) in the overall group and 94.4 pg/ML (s.d. 48.6) in the LC group at IP. %TE Intake (g/d) PROT FAT CHO GLU FRU NMES PROT FAT rrrrrrrrrrr −·214 ·623 ·635 −·326 −·491 ·448 ·699* ·686* ·742* −·606 −·496 ·143 ·637 ·937 ·427 −·059 ·722 ·980* ·967* ·919 ·998** −·080 Total kcal CHO NMES T LC CHO-Total carbohydrates, FAT-Total fat, FRU-Fructose, GLUC-Glucose, LC-low-carbohydrate, high-fat group, NMES-non-milk extrinsic sugars, PROT-protein, T – total, %TE – percentage total energy, *p < ·05 **p < ·005. In conclusion, low-carbohydrate diets provide the opportunity to assess responses to even small amounts of CHO, which are likely to be replaced in part by proteins. Despite low overall intakes of fructose and glucose in the LC group, strong and positive correlations with FGF21 levels were observed. The lower levels of FGF21 in the LC compared to the overall group are in line with findings that FGF21 levels are elevated with high-carbohydrate, low-protein diets with dietary fats having only minor impact(3). However, the majority of studies have still been undertaken using rodent models. The impact of dietary macronutrients on FGF21 levels as novel CMR marker in humans and the mechanism behind this relationship warrant further investigation. 1. Lakhani I, Gong M, Wong W et al. (2018) Metabolism 2018 Feb 1. pii: S0026-0495(18)30023-4. [Epub ahead of print]. 2. Jebb S, Lovegrove J, Griffin B et al. (2010) Am J Clin Nutr 92, 748–58. 3. Solon-Biet S, Cogger V, Pulpitel T et al. (2016) Cell Metab 24, 555–565

The Long-Term Future of Extragalactic Astronomy

If the current energy density of the universe is indeed dominated by a cosmological constant, then high-redshift sources will remain visible to us only until they reach some finite age in their rest-frame. The radiation emitted beyond that age will never reach us due to the acceleration of the cosmic expansion rate, and so we will never know what these sources look like as they become older. As a source image freezes on a particular time frame along its evolution, its luminosity distance and redshift continue to increase exponentially with observation time. The higher the current redshift of a source is, the younger it will appear as it fades out of sight. For the popular set of cosmological parameters, I show that a source at a redshift z=5-10 will only be visible up to an age of 4-6 billion years. Arguments relating the properties of high-redshift sources to present-day counterparts will remain indirect even if we continue to monitor these sources for an infinite amount of time. These sources will not be visible to us when they reach the current age of the universe.Comment: Phys. Rev. D, in press (2001

Macronutrient intake and prevalence of markers of metabolic syndrome in white UK adult males in the National Diet and Nutrition Survey Rolling Programme 2008–2014

The amount of carbohydrates recommended for consumption by current dietary guidelines has been challenged in relation to their suitability to prevent or manage cardiometabolic (CM) diseases with suggestions that they should be decreased and replaced by protein or fat( 1 , 2 ). Others have argued that a more personalised approach is required( 3 ). Aim of this investigation was to assess the potential impact of lower versus higher consumption of dietary macronutrients and prevalence of CM risk markers in a representative sample of the UK male white population. Unweighted data from 642 white adult males aged 19 and over in the National Diet and Nutrition Survey Rolling Programme( 4 ) (NDNS RP) 2008–2014 with or without metabolic syndrome (MetS)( 5 ) were analysed for associations of dietary macronutrient intake as percentage food energy (%FE) with CM risk markers. Logistic regression analysis (adjusted for age group and smoking status) was used to compare the odds ratios [OR] of prevalence of individual markers of MetS between the lowest and highest quartiles of dietary macronutrient intake as %FE (⩽44 vs. ≥52 for carbohydrates; ⩽31 vs. ≥39 for fats; ⩽15. vs. ≥19 for protein). There was a significant (p < 0·05) reduction in likelihood of MetS (OR, .55; 95 % confidence interval [CI], .34 to .84), and elevated waist circumference (OR, .50; 95 % CI, .30 to .83) and glucose levels (OR, .51; 95 % CI, .30 to .87) for those in the highest quartile of carbohydrate %FE intake compared to the lowest quartile, whereas those in the highest quartile of protein %FE intake had a significantly (p < 0·05) increased risk of presenting with the same markers of MetS (OR, 1·75; 95 % CI, 1·05 to 2·93; OR, 2·12; 95 % CI, 1·24 to 3·63; and OR, 2·15; 95 % CI, 1·25 to 3·70 respectively). Those with the highest compared to the lowest total dietary fat intake also presented with elevated CM risk markers, albeit these findings were not significant. *Metabolic Syndrome (MetS) definition: 3 out of 5 of the following: triglycerides (TRIG) ≥1·7 mmol/L; High-density lipoprotein cholesterol (HDL-C) ⩽1·03 mmol/L for males; Waist circumference (WC) ≥94 cm for white males; Glucose (GLUC) ≥5·6 mmol/L; Blood pressure (BP) ≥130 mmHg systolic or ≥85 mmHg diastolic respectively; CHO%FE – total carbohydrates percentage food energy; FAT%FE – total fats food energy; PROT%FE– total protein food energy; OR – odds ratio (adjusted for age group and smoking status), 1st vs. 4th quartile of intake; CI – confidence interval; a p < 0·05 Further investigations need to confirm whether the quality of the macronutrients consumed and overall diet quality( 6 ) has had an impact on these results. In the context of a personalised approach to nutrition future cohort studies should also provide data that allow for examining inter-individual variations in responses to dietary macronutrients, especially carbohydrates, to achieve optimum CM health for a larger proportion of the population

Dietary carbohydrate intake, visceral adipose tissue and associated markers of cardiometabolic risk

Risk of cardiometabolic (CM) disease is characterised by elevated visceral adipose tissue (VAT) and a number of associated biomar- kers(1). Some dietary carbohydrates (CHO) have been found to contribute to VAT accumulation(2). Little is known about the impact of following a low-carbohydrate diet versus a high-carbohydrate diet on VAT, adiponectin (ADPN), leptin (LEPT) and leptin:adipo- nectin ratio (LAR). The aim of this investigation was to assess the impact of dietary carbohydrates (CHO) on VAT and emerging CM risk markers in a sample of 10 healthy normal-weight and overweight Caucasian adults aged 32–60 (80 % male) at increased CM risk(3). This pilot study received ethical approval from Liverpool John Moores University Research Ethics Committee (16/ELS/ 029) and was registered with ClinicalTrials.gov (Ref. NCT03257085). Participants were randomly allocated to one of two groups and asked to either consume 50 % energy from CHO (high-carb (HC)) for a duration of 8 weeks. VAT was ana- lysed via bioelectrical impedance (SECA mBCA 515). Blood plasma samples were collected at baseline (BL), interim point (IP) and endpoint (EP) after a 12-hour overnight fast, immediately processed and frozen at -80°C. Thawed plasma samples were analysed via immunoassay technology (Randox Evidence InvestigatorTM Metabolic Syndrome Arrays I and II) for ADPN and LEPT levels. Statistical analysis was undertaken using IBM SPSS 24®. Parametric data was analysed via two-way mixed ANOVA; non-parametric data was analysed via Mann-Whitney U test and Friedman test. Average daily carbohydrate intake in the LC group was 44·2 g at IP and 48·9 g at EP. There were no significant differences between groups at any time point for ADPN, LEPT, LAR or VAT and no significant inter- actions for time or group*time for ADPN, LEPT or LAR. However, in the LC group VAT decreased significantly between baseline and endpoint by 15 % (p = ·015) Over the course of the intervention ADPN and LEPT decreased non- significantly (by 4 % and 70 % respectively) in the LC group, whilst increasing non-significantly in the HC group (9 % and 65 % respectively). LAR increased in the HC group throughout the study, whilst LAR in the LC group decreased albeit not significantly. VAT (litre) ADPN (ng/mL) LEPT (ng/mL) LAR BL IP EP Median Median Median M SD M SD M SD BL IP EP BL IP EP BL IP EP LC 4·1a 1·2 3·8 1·3 3·5a 1·2 8·9 8·6 8·5 3·96 1·64 1·20 0·45 0·19 0·14 HC 2·7 0·1 1·6 0·3 2·5 0·1 11·3 13·4 12·3 0·97 1·1 1·60 0·07 0·07 0·46 ADPN = adiponectin, BL = baseline, EP = endpoint, HC = high-carbohydrate, moderate fat diet, IP = interim point, LAR = leptin:adiponectin ratio, LEPT = leptin, LC = low-carbohydrate, high-fat diet, VAT = visceral adipose tissue, ap = ·015. NB: interquartile ranges not provided for median values due to missing data. Higher LAR has been found to be a marker of increased CM risk(4). In conclusion, while the significant reduction in VAT in the LC group corresponds with the reduction of LAR further evidence is required to corroborate these findings. Previous evidence for LC is supportive for improved CM health from various biomarkers(5); LAR should be considered as a useful endocrine addition for future LC studies. 1. Krasimira A, Mozaffarian D & Pischon T (2018) Clin Chem 64, 142–153. 2. Rüttgers D, Fischer K, Koch M et al. (2015) Br J Nutr 114, 1929–1940. 3. Jebb S, Lovegrove J, Griffin B et al. (2010) Am J Clin Nutr 92, 748–58. 4. López-Jaramillo P, Gómez-Arbeláez D, López-López J et al. (2014) Horm Mol Biol Clin Investig 18, 37–45. 5. Bazzano L, Hi T, Reynolds K et al. (2014) Ann Intern Med 161, 309–318

Rank change and growth within social hierarchies of the orange clownfish, Amphiprion percula

Social hierarchies within groups define the distribution of resources and provide benefits that support the collective group or favor dominant members. The progression of individuals through social hierarchies is a valuable characteristic for quantifying population dynamics. On coral reefs, some clownfish maintain size-based hierarchical communities where individuals queue through social ranks. The cost of waiting in a lower-ranked position is outweighed by the reduced risk of eviction and mortality. The orange clownfish, Amphiprion percula, maintains stable social groups with subordinate individuals queuing to be part of the dominant breeding pair. Strong association with their host anemone, complex social interactions, and relatively low predation rates make them ideal model organisms to assess changes in group dynamics through time in their natural environment. Here, we investigate the rank changes and isometric growth rates of A. percula from 247 naturally occurring social groups in Kimbe Island, Papua New Guinea (5° 12′ 13.54″ S, 150° 22′ 32.69″ E). We used DNA profiling to assign and track individuals over eight years between 2011 and 2019. Over half of the individuals survived alongside two or three members of their original social group, with twelve breeding pairs persisting over the study period. Half of the surviving individuals increased in rank and experienced double the growth rate of those that maintained their rank. Examining rank change in a wild fish population provides new insights into the complex social hierarchies of reef fishes and their role in social evolution

Clastic Polygonal Networks Around Lyot Crater, Mars: Possible Formation Mechanisms From Morphometric Analysis

Polygonal networks of patterned ground are a common feature in cold-climate environments. They can form through the thermal contraction of ice-cemented sediment (i.e. formed from fractures), or the freezing and thawing of ground ice (i.e. formed by patterns of clasts, or ground deformation). The characteristics of these landforms provide information about environmental conditions. Analogous polygonal forms have been observed on Mars leading to inferences about environmental conditions. We have identified clastic polygonal features located around Lyot crater, Mars (50°N, 30°E). These polygons are unusually large (> 100 m diameter) compared to terrestrial clastic polygons, and contain very large clasts, some of which are up to 15 metres in diameter. The polygons are distributed in a wide arc around the eastern side of Lyot crater, at a consistent distance from the crater rim. Using high-resolution imaging data, we digitised these features to extract morphological information. These data are compared to existing terrestrial and Martian polygon data to look for similarities and differences and to inform hypotheses concerning possible formation mechanisms. Our results show the clastic polygons do not have any morphometric features that indicate they are similar to terrestrial sorted, clastic polygons formed by freeze-thaw processes. They are too large, do not show the expected variation in form with slope, and have clasts that do not scale in size with polygon diameter. However, the clastic networks are similar in network morphology to thermal contraction cracks, and there is a potential direct Martian analogue in a sub-type of thermal contraction polygons located in Utopia Planitia. Based upon our observations, we reject the hypothesis that polygons located around Lyot formed as freeze-thaw polygons and instead an alternative mechanism is put forward: they result from the infilling of earlier thermal contraction cracks by wind-blown material, which then became compressed and/or cemented resulting in a resistant fill. Erosion then leads to preservation of these polygons in positive relief, while later weathering results in the fracturing of the fill material to form angular clasts. These results suggest that there was an extensive area of ice-rich terrain, the extent of which is linked to ejecta from Lyot crater

The impact of nature of onset of pain and posttraumatic stress on adjustment to chronic pain and treatment outcome

Despite the demonstrated efficacy of cognitive-behavioural therapy for chronic pain, recent research has attempted to identify predictors of treatment outcome in order to improve the effectiveness of such treatments. This research has indicated that variables such as the nature of the onset of the pain and psychopathology are associated with poor adjustment to chronic pain. Accordingly, these variables might also be predictive of poor response to treatment. Individuals who experience a sudden onset of pain following an injury or accident, particularly when the instigating event is experienced as psychologically traumatic, may present for treatment with high levels of distress, including symptoms consistent with a posttraumatic stress response. The impact of this type of onset of pain and posttraumatic stress symptoms on adjustment to chronic pain and treatment outcome is the focus of this thesis. Three studies were conducted to clarify and extend earlier research findings in this area. Using 536 patients referred for treatment in a tertiary referral pain management centre, the first study examined the psychometric properties of a widely used self-report measure of posttraumatic stress symptoms (the PTSD Checklist, or PCL), modified for use in a chronic pain sample. This study provided preliminary support for the suitability of the PCL as a self-report measure of Posttraumatic Stress Disorder (PTSD) symptoms in chronic pain patients. However, the study also highlighted a number of issues with the use of self-report measures of posttraumatic stress symptoms in chronic pain patient samples. In particular, PCL items enquiring about symptoms which are a common aspect of the chronic pain experience (e.g. irritability, sleep problems) appeared to contribute to high mean scores on the PCL Avoidance and Arousal subscales. Furthermore, application of diagnostic cut-off scores and an algorithm recommended for the PCL in other trauma groups suggested that a much larger proportion of the sample was identified as potentially meeting diagnostic criteria for PTSD than would have been expected from previous research. The second study utilised the modified PCL to investigate the impact of different types of onset of pain (e.g. traumatic onset) and posttraumatic stress symptoms on adjustment to chronic pain in a sample of 196 chronic pain patients referred to the same centre. For patients who experienced the onset of pain related to a specific event, two independent experts in the field of PTSD determined whether these events satisfied the definition of a traumatic event according to DSM-IV diagnostic criteria. Adjustment was assessed through a number of validated measures of mood, disability, pain experience, and pain-related cognitions. Contrary to expectations, comparisons between patients who had experienced different types of onset of pain revealed few significant differences between them. That is, analyses comparing patients presenting with accident-related pain, or pain related to other specific events, to patients who had experienced spontaneous or insidious onset of pain revealed no significant differences between the groups on measures of pain severity, pain-related disability, and symptoms of affective distress after adjustment for age, pain duration, and compensation status. Similarly, comparisons between patients who had experienced a potentially traumatic onset of pain with those who had experienced a non-traumatic or spontaneous or insidious onset of pain also revealed no significant differences on the aforementioned variables. In contrast, compensation status, age, and a number of cognitive variables were significant predictors of pain severity, pain-related disability, and depression. The final study investigated the impact of type of pain onset and posttraumatic stress symptoms on response to a multidisciplinary cognitive-behavioural pain management program. Unlike the previous study, this treatment outcome study revealed a number of differences between onset groups. Most notably, patients who had experienced an insidious or spontaneous onset of pain reported greater improvements in pain severity and maintained these improvements more effectively over a one month period than patients who had experienced pain in the context of an accident or other specific incident. There was also limited evidence that improvements in depression favoured patients who had experienced an insidious or spontaneous and non-traumatic onset of pain. Consistent with this, posttraumatic stress symptoms were a significant predictor of treatment outcome, with higher levels of symptoms being associated with smaller improvements in pain-related disability and distress. Notably, this study also revealed that certain cognitive variables (i.e. catastrophising, self-efficacy, and fear-avoidance beliefs) were also significant predictors of treatment outcome, consistent with previous findings in the pain literature. This provided some perspective on the relative roles of both PTSD symptoms and cognitive variables in adjustment to persisting pain and treatment response. These findings were all consistent with expectations and with previous research. Implications for future research and for the assessment and treatment of chronic pain patients who present with posttraumatic stress symptoms are discussed