Rats distinguish between absence of events and lack of evidence in contingency learning.

The goal of three experiments was to study whether rats are aware of the difference between absence of events and lack of evidence. We used a Pavlovian extinction paradigm in which lights consistently signaling sucrose were suddenly paired with the absence of sucrose. The crucial manipulation involved the absent outcomes in the extinction phase. Whereas in the Cover conditions, access to the drinking receptacle was blocked by a metal plate, in the No Cover conditions, the drinking receptacle was accessible. The Test phase showed that in the Cover conditions, the measured expectancies of sucrose were clearly at a higher level than in the No Cover conditions. We compare two competing theories potentially explaining the findings. A cognitive theory interprets the observed effect as evidence that the rats were able to understand that the cover blocked informational access to the outcome information, and therefore the changed learning input did not necessarily signify a change of the underlying contingency in the world. An alternative associationist account, renewal theory, might instead explain the relative sparing of extinction in the Cover condition as a consequence of context change. We discuss the merits of both theories as accounts of our data and conclude that the cognitive explanation is in this case preferred

On the Energy Dependence of the Dipole-Proton Cross Section in Deep Inelastic Scattering

We study the dipole picture of high-energy virtual-photon-proton scattering. It is shown that different choices for the energy variable in the dipole cross section used in the literature are not related to each other by simple arguments equating the typical dipole size and the inverse photon virtuality, contrary to what is often stated. We argue that the good quality of fits to structure functions that use Bjorken-x as the energy variable - which is strictly speaking not justified in the dipole picture - can instead be understood as a consequence of the sign of scaling violations that occur for increasing Q^2 at fixed small x. We show that the dipole formula for massless quarks has the structure of a convolution. From this we obtain derivative relations between the structure function F_2 at large and small Q^2 and the dipole-proton cross section at small and large dipole size r, respectively.Comment: 27 page

A time study of physicians' work in a German university eye hospital to estimate unit costs.

BACKGROUND: Technical efficiency of hospital services is debated since performance has been heterogeneous. Staff time represents the main resource in patient care and its inappropriate allocation has been identified as a key factor of inefficiency. The aim of this study was to analyse the utilisation of physicians' work time stratified by staff groups, tasks and places of work. A further aim was to use these data to estimate resource use per unit of output. METHODS: A self-reporting work-sampling study was carried during 14-days at a University Eye Hospital. Staff costs of physicians per unit of output were calculated at the wards, the operating rooms and the outpatient unit. RESULTS: Forty per cent of total work time was spent in contact with the patient. Thirty per cent was spent with documentation tasks. Time spent with documentation tasks declined monotonically with increasing seniority of staff. Unit costs were 56 € per patient day at the wards, 77 € and 20 € per intervention at the operating rooms for inpatients and outpatients, respectively, and 33 € per contact at the outpatient unit. Substantial differences in resources directly dedicated to the patient were found between these locations. CONCLUSION: The presented data provide unprecedented units costs in inpatient Ophthalmology. Future research should focus on analysing factors that influence differences in time allocation, such as types of patients, organisation of care processes and composition of staff

Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08 x 10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases

A comparison of ultrasound measurements to assess carotid atherosclerosis development in subjects with and without type 2 diabetes

BACKGROUND: Subjects with type 2 diabetes are at an increased risk of vascular complications. The use of carotid ultrasound remains an attractive, non-invasive method to monitor atherosclerotic disease progression and/or response to treatment in patients with type 2 diabetes, with intima-media thickness routinely used as the gold standard to detect pathology. However, alternative measurements, such as plaque area or volume, may represent a potentially more powerful approach. Thus, the objective of this study was to compare the traditional intima-media thickness measurement against the novel total plaque volume measurement in analyzing carotid atherosclerosis development in individuals with type 2 diabetes. METHODS: The case-control study included 49 Oji-Cree adults with diabetes or impaired glucose tolerance, aged 21–69, and 49 sex- and age-matched normoglycemic subjects. At baseline, metabolic variables were measured, including body mass index, waist circumference, total cholesterol:high density lipoprotein ratio, plasma triglycerides, plasma glucose, and serum insulin. Carotid ultrasound measurements, 7 years later, assessed carotid arterial intima-media thickness and total plaque volume. RESULTS: At baseline, the two groups were well matched for smoking habits, hypertension, body mass index, and waist circumference. Differences were noted in baseline measurements of total cholesterol:high density lipoprotein (P = 0.0006), plasma triglycerides (P < 0.0001) and fasting glucose (P < 0.0001). After seven years, carotid ultrasound scans revealed that total plaque volume measurements (P = 0.037), but not intima-media thickness measurements, were higher in subjects with diabetes/impaired glucose tolerance compared to the normoglycemic controls. Correlation between intima-media thickness and total plaque volume was moderate. Based on our study findings, to achieve power levels >0.70 when comparing intima-media thickness measurements for diabetics versus non-diabetics, thousands of study subjects are required. For comparing total plaque volume measurements, only hundreds of study subjects are required. CONCLUSION: The development of atherosclerotic plaque is greater in subjects with diabetes/impaired glucose tolerance. Total plaque volume appears to capture the atherosclerotic disease burden more effectively in subjects with type 2 diabetes, and would be an appropriate outcome measure for studies aimed at changing the diabetic milieu