The wider context of the Lower Jurassic Toarcian oceanic anoxic event in Yorkshire coastal outcrops, UK

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.The Toarcian Oceanic Anoxic Event (T-OAE, ∼183 Ma) was characterized by enhanced carbon burial, a prominent negative carbon-isotope excursion (CIE) in marine carbonate and organic matter, and numerous geochemical anomalies. A precursor excursion has also been documented at the Pliensbachian/Toarcian boundary, but its possible causes are less constrained. The T-OAE is intensively studied in the Cleveland Basin, Yorkshire, UK, whose sedimentary deposits have been litho-, bio- and chemostratigraphically characterised. Here, we present new elemental data produced by hand-held X-ray fluorescence analysis to test the expression of redox-sensitive trace metals and detrital elements across the upper Pliensbachian to mid-Toarcian of the Cleveland Basin. Detrital elemental concentrations (Al, Si, Ti, Zr) are used as proxies for siliciclastic grain content and thus, sea-level change, which match previous sequence stratigraphic interpretations from the Cleveland Basin. The timescale of the event is debated, though our new elemental proxies of relative sea level change show evidence for a cyclicity of 350 cm that may be indicative of ∼405 kyr eccentricity cycles in Yorkshire. Trends in total organic carbon and redox-sensitive elements (S, Fe, Mo, As) confirm scenarios of widespread ocean deoxygenation across the T-OAE. The correlation of comparable trends in Mo across the T-OAE in Yorkshire and the Paris Basin suggests a similar oceanic drawdown of this element accompanying widespread anoxia in the two basins. Data from Yorkshire point to a transgressive trend at the time of the Mo drawdown, which contradicts the “basin restriction” model for the euxinic conditions that characterise the CIE interval.The Carlsberg Foundation (project 2011-01-0737 to CK) and the Danish Council for Independent Research-Natural Sciences (project 09-072715 to CK) are acknowledged for contributions to financing this project

Compensatory changes in energy balance during dapagliflozin treatment in type 2 diabetes mellitus: a randomised double-blind, placebo-controlled, cross-over trial (ENERGIZE)-study protocol.

INTRODUCTION: Sodium glucose cotransporter 2 (SGLT2) inhibitors are effective blood-glucose-lowering medications with beneficial effects on body weight in patients with type 2 diabetes mellitus (T2DM). However, observed weight loss is less than that predicted from quantified glycosuria, suggesting a compensatory increase in energy intake or a decrease in energy expenditure. Studies using dual-energy X-ray absorptiometry (DEXA) have suggested most body weight change is due to loss of adipose tissue, but organ-specific changes in fat content (eg, liver, skeletal muscle) have not been determined. In this randomised, double-blind, placebo-controlled crossover study, we aim to study the compensatory changes in energy intake, eating behaviour and energy expenditure accompanying use of the SGLT2 inhibitor, dapagliflozin. Additionally, we aim to quantify changes in fat distribution using MRI, in liver fat using proton magnetic resonance spectroscopy ((1)H-MRS) and in central nervous system (CNS) responses to food images using blood oxygen level dependent (BOLD) functional MRI (fMRI). METHODS AND ANALYSIS: This outpatient study will evaluate the effect of dapagliflozin (10 mg), compared with placebo, on food intake and energy expenditure at 7 days and 12 weeks. 52 patients with T2DM will be randomised to dapagliflozin or placebo for short-term and long-term trial interventions in a within participants, crossover design. The primary outcome is the difference in energy intake during a test meal between dapagliflozin and placebo. Intake data are collected automatically using a customised programme operating a universal eating monitor (UEM). Secondary outcomes include (1) measures of appetite regulation including rate of eating, satiety quotient, appetite ratings (between and within meals), changes in CNS responses to food images measured using BOLD-fMRI, (2) measures of energy expenditure and (3) changes in body composition including changes in liver fat and abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). ETHICAL APPROVAL: This study has been approved by the North West Liverpool Central Research Ethics Committee (14/NW/0340) and is conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice (GCP). TRIAL REGISTRATION NUMBER: ISRCTN14818531. EUDRACT number 2013-004264-60

Patterns of muscle coordination during dynamic glenohumeral joint elevation: An EMG study

The shoulder relies heavily on coordinated muscle activity for normal function owing to its limited osseous constraint. However, previous studies have failed to examine the sophisticated interrelationship between all muscles. It is essential for these normal relationships to be defined as a basis for understanding pathology. Therefore, the primary aim of the study was to investigate shoulder inter-muscular coordination during different planes of shoulder elevation. Twenty healthy subjects were included. Electromyography was recorded from 14 shoulder girdle muscles as subjects performed shoulder flexion, scapula plane elevation, abduction and extension. Cross-correlation was used to examine the coordination between different muscles and muscle groups. Significantly higher coordination existed between the rotator cuff and deltoid muscle groups during the initial (Pearson Correlation Coefficient (PCC) = 0.79) and final (PCC = 0.74) stages of shoulder elevation compared to the mid-range (PCC = 0.34) (p = 0.020–0.035). Coordination between the deltoid and a functional adducting group comprising the latissimus dorsi and teres major was particularly high (PCC = 0.89) during early shoulder elevation. The destabilising force of the deltoid, during the initial stage of shoulder elevation, is balanced by the coordinated activity of the rotator cuff, latissimus dorsi and teres major. Stability requirements are lower during the mid-range of elevation. At the end-range of movement the demand for muscular stability again increases and higher coordination is seen between the deltoid and rotator cuff muscle groups. It is proposed that by appreciating the sophistication of normal shoulder function targeted evidence-based rehabilitation strategies for conditions such as subacromial impingement syndrome or shoulder instability can be developed

A functional Magnetic Resonance Imaging study of patients with Polar Type II/III complex shoulder instability

The pathophysiology of Stanmore Classification Polar type II/III shoulder instability is not well understood. Functional Magnetic Resonance Imaging was used to measure brain activity in response to forward flexion and abduction in 16 patients with Polar Type II/III shoulder instability and 16 age-matched controls. When a cluster level correction was applied patients showed significantly greater brain activity than controls in primary motor cortex (BA4), supramarginal gyrus (BA40), inferior frontal gyrus (BA44), precentral gyrus (BA6) and middle frontal gyrus (BA6): the latter region is considered premotor cortex. Using voxel level correction within these five regions a unique activation was found in the primary motor cortex (BA4) at MNI coordinates -38 -26 56. Activation was greater in controls compared to patients in the parahippocampal gyrus (BA27) and perirhinal cortex (BA36). These findings show, for the first time, neural differences in patients with complex shoulder instability, and suggest that patients are in some sense working harder or differently to maintain shoulder stability, with brain activity similar to early stage motor sequence learning. It will help to understand the condition, design better therapies and improve treatment of this group; avoiding the common clinical misconception that their recurrent shoulder dislocations are a form of attention-seeking

Lyotropic 'hairy' TiO2 nanorods

We report the synthesis of the first stable, solution-processable and photocrosslinkable hybrid organic/ inorganic titanium dioxide nanorods as ‘hairy rods’ coated with phosphonate ligands with photoreactive coumarin groups located in a terminal position. The relationships between the chemical structure of the diethyl-u-[(7-oxycoumaryl)-n-alkyl]phosphonate ligands on the ligand exchange rate (LER) and the solubility of the resultant ligand-stabilized titanium dioxide nanorods in organic solvents are elucidated. These TiO2 nanorods, with an organic ligand coating, are short enough (aspect ratio ¼ 5–8) to be dissolved in chlorobenzene at high concentrations, but long enough to form lyotropic nematic liquid crystals. These colloidal solutions are used to deposit a thin, uniform layer of hybrid organic/inorganic TiO2 nanorods with their long axes in the plane of a flat, smooth substrate through a self-organization process. Standard photolithographic patterning creates an insoluble dielectric layer of the desired thickness, smoothness and uniformity and with a dielectric constant of sufficient magnitude, k ¼ 8, suitable for the fabrication of multilayer, plastic electronic devices using solution-based fabrication techniques, such as ink-jet printing, used in roll-to-roll manufacturing

Consensus on a video analysis framework of descriptors and definitions by the Rugby Union Video Analysis Consensus group

Using an expert consensus-based approach, a rugby union Video Analysis Consensus (RUVAC) group was formed to develop a framework for video analysis research in rugby union. The aim of the framework is to improve the consistency of video analysis work in rugby union and help enhance the overall quality of future research in the sport. To reach consensus, a systematic review and Delphi method study design was used. After a systematic search of the literature, 17 articles were used to develop the final framework that described and defined key actions and events in rugby union (rugby). Thereafter, a group of researchers and practitioners with experience and expertise in rugby video analysis formed the RUVAC group. Each member of the group examined the framework of descriptors and definitions and rated their level of agreement on a 5-point agreement Likert scale (1: strongly disagree; 2: disagree; 3: neitheragree or disagree; 4: agree; 5: strongly agree). The mean rating of agreement on the five-point scale (1: strongly disagree; 5: strongly agree) was 4.6 (4.3–4.9), 4.6 (4.4–4.9), 4.7 (4.5–4.9), 4.8 (4.6–5.0) and 4.8 (4.6–5.0) for the tackle, ruck, scrum, line-out and maul, respectively. The RUVAC group recommends using this consensus as the starting framework when conducting rugby video analysis research. Which variables to use (if not all) depends on the objectives of the study. Furthermore, the intention of this consensus is to help integrate video data with other data (eg, injury surveillance)

Lipidomics Reveals Early Metabolic Changes in Subjects with Schizophrenia: Effects of Atypical Antipsychotics

There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease. © 2013 McEvoy et al

The Impact of Global Warming and Anoxia on Marine Benthic Community Dynamics: an Example from the Toarcian (Early Jurassic)

The Pliensbachian-Toarcian (Early Jurassic) fossil record is an archive of natural data of benthic community response to global warming and marine long-term hypoxia and anoxia. In the early Toarcian mean temperatures increased by the same order of magnitude as that predicted for the near future; laminated, organic-rich, black shales were deposited in many shallow water epicontinental basins; and a biotic crisis occurred in the marine realm, with the extinction of approximately 5% of families and 26% of genera. High-resolution quantitative abundance data of benthic invertebrates were collected from the Cleveland Basin (North Yorkshire, UK), and analysed with multivariate statistical methods to detect how the fauna responded to environmental changes during the early Toarcian. Twelve biofacies were identified. Their changes through time closely resemble the pattern of faunal degradation and recovery observed in modern habitats affected by anoxia. All four successional stages of community structure recorded in modern studies are recognised in the fossil data (i.e. Stage III: climax; II: transitional; I: pioneer; 0: highly disturbed). Two main faunal turnover events occurred: (i) at the onset of anoxia, with the extinction of most benthic species and the survival of a few adapted to thrive in low-oxygen conditions (Stages I to 0) and (ii) in the recovery, when newly evolved species colonized the re-oxygenated soft sediments and the path of recovery did not retrace of pattern of ecological degradation (Stages I to II). The ordination of samples coupled with sedimentological and palaeotemperature proxy data indicate that the onset of anoxia and the extinction horizon coincide with both a rise in temperature and sea level. Our study of how faunal associations co-vary with long and short term sea level and temperature changes has implications for predicting the long-term effects of “dead zones” in modern oceans

Ku70/80 gene expression and DNA-dependent protein kinase (DNA-PK) activity do not correlate with double-strand break (dsb) repair capacity and cellular radiosensitivity in normal human fibroblasts

The expression of the Ku70 and Ku80 genes as well as the activity of the DNA-dependent protein kinase (DNA-PK) were studied in 11 normal human fibroblast lines. The proteins studied are known to be part of a double-strand break (dsb) repair complex involved in non-homologous recombination, as was demonstrated for the radiosensitive rodent mutant cell lines of the complementation groups 5–7. The 11 fibroblast lines used in this study represent a typical spectrum of normal human radiosensitivity with the surviving fraction measured for a dose of 3.5 Gy, SF3.5 Gy, ranging from 0.03 to 0.28. These differences in cell survival were previously shown to correlate with the number of non-repaired dsbs. We found that the mRNA signal intensities of both Ku70 and Ku80 genes were fairly similar for the 11 cell lines investigated. In addition, the DNA-PK activity determined by the pulldown assay was fairly constant in these fibroblast lines. Despite the correlation between cell survival and dsb repair capacity, there was no correlation between dsb repair capacity and DNA-PK activity in the tested normal human fibroblast lines. Obviously, in this respect, other proteins/pathways appear to be more relevant. © 1999 Cancer Research Campaig