Pendsé, DA; Makanyanga, JC; Plumb, AA; Bhatnagar, G; Atkinson, D; Rodriguez-Justo, M; Halligan, S; Taylor, SA
PURPOSE: To evaluate whether the extent of enteric diffusion-weighted imaging (DWI) signal abnormality reflects inflammatory burden in Crohn's disease (CD), and to compare qualitative and quantitative grading. METHODS: 69 CD patients (35 male, age 16-78) undergoing MR enterography with DWI (MRE-D) and the same-day faecal calprotectin (cohort 1) were supplemented by 29 patients (19 male, age 16-70) undergoing MRE-D and terminal ileal biopsy (cohort 2). Global (cohort 1) and terminal ileal (cohort 2) DWI signal was graded (0 to 3) by 2 radiologists and segmental apparent diffusion coefficient (ADC) calculated. Data were compared to calprotectin and a validated MRI activity...
Matsumoto, R; Evans, SE
The presence of a palatal dentition is generally considered to be the primitive condition in amniotes, with each major lineage showing a tendency toward reduction. This study highlights the variation in palatal tooth arrangements and reveals clear trends within the evolutionary history of tetrapods. Major changes occurred in the transition between early tetrapods and amphibians on the one hand, and stem amniotes on the other. These changes reflect the function of the palatal dentition, which can play an important role in holding and, manipulating food during feeding. Differences in the arrangement of palatal teeth, and in their pattern of loss,...
Rothschild, DH; Spectre, L
We present a puzzle about knowledge, probability and conditionals. We show that in certain cases some basic and plausible principles governing our reasoning come into conflict. In particular, we show that there is a simple argument that a person may be in a position to know a conditional the consequent of which has a low probability conditional on its antecedent, contra Adams’ Thesis. We suggest that the puzzle motivates a very strong restriction on the inference of a conditional from a disjunction.
Swindells, MB; Porter, CT; Couch, M; Hurst, J; Abhinandan, KR; Nielsen, JH; Macindoe, G; Hetherington, J; Martin, AC
abYsis is a web-based antibody research system that includes an integrated database of antibody sequence and structure data. The system can be interrogated in numerous ways-from simple text and sequence searches to sophisticated queries that apply 3D structural constraints. The publicly available version includes pre-analyzed sequence data from the European Molecular Biology Laboratory European Nucleotide Archive (EMBL-ENA) and Kabat as well as structure data from the Protein Data Bank. A researcher's own sequences can also be analyzed through the web interface. A defining characteristic of abYsis is that the sequences are automatically numbered with a series of popular schemes such...
Chahboun, S; Flumini, A; Pérez González, C; McManus, IC; Santiago, J
Does reading and writing direction (RWD) influence the aesthetic appreciation of photography? Pérez González showed that nineteenth-century Iranian and Spanish professional photographers manifest lateral biases linked to RWD in their compositions. The present study aimed to test whether a population sample showed similar biases. Photographs with left-to-right (L-R) and right-to-left (R-L) directionality were selected from Pérez González's collections and presented in both original and mirror-reversed forms to Spanish (L-R readers) and Moroccan (R-L readers) participants. In Experiment 1, participants rated each picture for its aesthetic pleasingness. The results showed neither effects of lateral organization nor interactions with RWD. In Experiment...
Wu, JW; Hussaini, SA; Bastille, IM; Rodriguez, GA; Mrejeru, A; Rilett, K; Sanders, DW; Cook, C; Fu, H; Boonen, RA; Herman, M; Nahmani, E; Emrani, S; Figueroa, YH; Diamond, MI; Clelland, CL; Wray, S; Duff, KE
Tau protein can transfer between neurons transneuronally and trans-synaptically, which is thought to explain the progressive spread of tauopathy observed in the brain of patients with Alzheimer's disease. Here we show that physiological tau released from donor cells can transfer to recipient cells via the medium, suggesting that at least one mechanism by which tau can transfer is via the extracellular space. Neuronal activity has been shown to regulate tau secretion, but its effect on tau pathology is unknown. Using optogenetic and chemogenetic approaches, we found that increased neuronal activity stimulates the release of tau in vitro and enhances tau...
Brownlee, W; Altmann, DR; Alves Da Mota, P; Swanton, JK; Miszkeil, KA; Wheeler-Kingshott, CAM; Ciccarelli, O; Miller, DH
BACKGROUND: Spinal cord pathology is an important substrate for long-term disability in multiple sclerosis (MS). OBJECTIVE: To investigate longitudinal changes in spinal cord lesions and atrophy in patients with a non-spinal clinically isolated syndrome (CIS), and how they relate to the development of disability. METHODS: In all, 131 patients with a non-spinal CIS had brain and spinal cord imaging at the time of CIS and approximately 5 years later (median: 5.2 years, range: 3.0–7.9 years). Brain magnetic resonance imaging (MRI) measures consisted of T2-hyperintense and T1-hypointense lesion loads plus brain atrophy. Spinal cord MRI measures consisted of lesion number and the upper cervical...
It is often said that English law does not impose “remedial” constructive
trusts because it is manifestly inappropriate and fundamentally
unjustified to impose trusts through the exercise of judicial discretion and
with retrospective effect. This paper observes the definitional deficiencies in
this understanding, and reanalyses constructive trusts in terms of the rights
which they give effect to. This understanding reveals that English law sets
its face against the exercise of discretion in relation only to some “remedial”
constructive trusts and not others, and that the perceived difficulties with remedial
constructive trusts are often exaggerated. It ends by noting some crucial
implications of the re-analysis for the future development of...
Lo, SH; Waller, J; Vrinten, C; Wardle, J; von Wagner, C
Objective To compare self-reported with objectively recorded participation in Faecal Occult Blood testing (FOBt) colorectal cancer (CRC) screening in a national programme.
Methods Survey respondents living in England who were eligible for screening were asked in face-to-face interviews if they had ever been invited to do a CRC screening test, how many times they had been invited, and how many times they had participated. National Health Service (NHS) Bowel Cancer Screening Programme (BCSP) records were consulted for respondents who had consented to a record check. The outcome measures were ‘ever uptake’ (responded to ≥1 invitation), ‘repeat uptake’ (responded to ≥2 invitations),...
Demakakos, P; Biddulph, JP; Bobak, M; Marmot, MG
BACKGROUND: Despite the importance of socioeconomic position for survival, total wealth, which is a measure of accumulation of assets over the life course, has been underinvestigated as a predictor of mortality. We investigated the association between total wealth and mortality at older ages.
METHODS: We estimated Cox proportional hazards models using a sample of 10 305 community-dwelling individuals aged ≥50 years from the English Longitudinal Study of Ageing.
RESULTS: 2401 deaths were observed over a mean follow-up of 9.4 years. Among participants aged 50-64 years, the fully adjusted HRs for mortality were 1.21 (95% CI 0.92 to 1.59) and 1.77 (1.35 to 2.33) for those...
Vinckier, F; Gaillard, R; Palminteri, S; Rigoux, L; Salvador, A; Fornito, A; Adapa, R; Krebs, MO; Pessiglione, M; Fletcher, PC
A state of pathological uncertainty about environmental regularities might represent a key step in the pathway to psychotic illness. Early psychosis can be investigated in healthy volunteers under ketamine, an NMDA receptor antagonist. Here, we explored the effects of ketamine on contingency learning using a placebo-controlled, double-blind, crossover design. During functional magnetic resonance imaging, participants performed an instrumental learning task, in which cue-outcome contingencies were probabilistic and reversed between blocks. Bayesian model comparison indicated that in such an unstable environment, reinforcement learning parameters are downregulated depending on confidence level, an adaptive mechanism that was specifically disrupted by ketamine administration. Drug...
Worbe, Y; Palminteri, S; Savulich, G; Daw, ND; Fernandez-Egea, E; Robbins, TW; Voon, V
Human decision-making arises from both reflective and reflexive mechanisms, which underpin goal-directed and habitual behavioural control. Computationally, these two systems of behavioural control have been described by different learning algorithms, model-based and model-free learning, respectively. Here, we investigated the effect of diminished serotonin (5-hydroxytryptamine) neurotransmission using dietary tryptophan depletion (TD) in healthy volunteers on the performance of a two-stage decision-making task, which allows discrimination between model-free and model-based behavioural strategies. A novel version of the task was used, which not only examined choice balance for monetary reward but also for punishment (monetary loss). TD impaired goal-directed (model-based) behaviour in the...
Day, AC; Donachie, PH; Sparrow, JM; Johnston, RL
To describe the outcomes of cataract surgery in the United Kingdom.
Anonymised data on 180 114 eyes from 127 685 patients undergoing cataract surgery between August 2006 and November 2010 were collected prospectively from 28 sites. Outcome measures included intraoperative and postoperative complication rates, and preoperative and postoperative visual acuities.
Median age at first eye surgery was 77.1 years, 36.9% cases had ocular co-pathology and 41.0% patients underwent cataract surgery on both eyes. Preoperative visual acuity was 0.30 logMAR or better in 32.0% first eyes and 47.7% second eyes. Postoperative best-measured visual acuity was 0.00 and 0.30 logMAR or better in 50.8...
Brown, J; Michie, S; Walmsley, M; West, R
Online motivational films to promote quit attempts could encourage large numbers of smokers to stop at low unit cost. We evaluated an online film documenting the experiences of smokers who recorded the first month of their successful attempts to quit (4Weeks2Freedom). The film was designed to boost motivation and self-efficacy and provide role-models to promote ex-smoker identities.
Miesfeld, JB; Gestri, G; Clark, BS; Flinn, MA; Poole, RJ; Bader, JR; Besharse, JC; Wilson, SW; Link, BA
The optic vesicle comprises a pool of bi-potential progenitor cells from which the retinal pigment epithelium (RPE) and neural retina fates segregate during ocular morphogenesis. Several transcription factors and signaling pathways have been shown to be important for RPE maintenance and differentiation, but an understanding of the initial fate specification and determination of this ocular cell type is lacking. We show that Yap/Taz-Tead activity is necessary and sufficient for optic vesicle progenitors to adopt RPE identity in zebrafish. A Tead-responsive transgene is expressed within the domain of the optic cup from which RPE arises, and Yap immunoreactivity localizes to the...
Abstract This paper briefly reviews the physical and human geography of the Kamchatka region and summarises previous research on Holocene climate dynamics. We provide context for the rest of the Special Issue of the Journal Global and Planetary Change entitled ‘Holocene climate change in Kamchatka’, the primary focus of which is the use of lake sediment records for palaeoclimatic inferences. In this paper an additional perspective from ongoing tree ring, ice core and borehole temperature reconstructions illustrates that The Kamchatka region is rich in paleoclimatic proxies. The period of the last 200 years is sufficiently covered by the proxy information,...
D'Ostilio, K; Goetz, SM; Hannah, R; Ciocca, M; Chieffo, R; Chen, JC; Peterchev, AV; Rothwell, JC
OBJECTIVE: To compare the strength–duration (S–D) time constants of motor cortex structures activated by current pulses oriented posterior–anterior (PA) or anterior–posterior (AP) across the central sulcus.
METHODS: Motor threshold and input–output curve, along with motor evoked potential (MEP) latencies, of first dorsal interosseus were determined at pulse widths of 30, 60, and 120 μs using a controllable pulse parameter (cTMS) device, with the coil oriented PA or AP. These were used to estimate the S–D time constant and we compared with data for responses evoked by cTMS of the ulnar nerve at the elbow.
RESULTS: The S–D time constant with PA was...
van de Pavert, SH; Muhlert, N; Sethi, V; Wheeler-Kingshott, CA; Ridgway, GR; Geurts, JJ; Ron, M; Yousry, TA; Thompson, AJ; Miller, DH; Chard, DT; Ciccarelli, O
The extent and clinical relevance of grey matter (GM) pathology in multiple sclerosis (MS) are increasingly recognised. GM pathology may present as focal lesions, which can be visualised using double inversion recovery (DIR) MRI, or as diffuse pathology, which can manifest as atrophy. It is, however, unclear whether the diffuse atrophy centres on focal lesions. This study aimed to determine if GM lesions and GM atrophy colocalise, and to assess their independent relationship with motor and cognitive deficits in MS.
Wells, JC; Haroun, D; Williams, JE; Nicholls, D; Darch, T; Eaton, S; Fewtrell, MS
Whether fat-free mass (FFM) and its components are depleted in eating-disorder (ED) patients is uncertain. Dual energy X-ray absorptiometry (DXA) is widely used to assess body composition in pediatric ED patients; however, its accuracy in underweight populations remains unknown. We aimed (1) to assess body composition of young females with ED involving substantial weight loss, relative to healthy controls using the four-component (4C) model, and (2) to explore the validity of DXA body composition assessment in ED patients.
Sun, G; Hu, X; Sinclair, HD; BouDagher-Fadel, MK; Wang, J
The tectonic evolution of the Lhasa terrane (southern Tibetan Plateau) played a fundamental role in the formation of the Tibetan Plateau. However, many uncertainties remain with regard to the tectonic and paleogeographic evolution of the Lhasa terrane prior to the India-Asia collision. To determine the early tectonic processes that controlled the topographic evolution of the Lhasa terrane, we analyze the Cretaceous strata exposed in the Coqen Basin (northern Lhasa subterrane), which comprises the Langshan and Daxiong Formations. The Langshan Formation unconformably overlies the volcanic rocks of the Lower Cretaceous Zelong Group and consists of ~80 m of Orbitolina-bearing limestones, which...