Collateral fattening in body composition autoregulation: its determinants and significance for obesity predisposition

Collateral fattening refers to the process whereby excess fat is deposited as a result of the body’s attempt to counter a deficit in lean mass through overeating. Its demonstration and significance to weight regulation and obesity can be traced to work on energy budget strategies in growing mammals and birds, and to men recovering from experimental starvation. The cardinal features of collateral fattening rests upon (i) the existence of a feedback system between lean tissue and appetite control, with lean tissue deficit driving hyperphagia, and (ii) upon the occurrence of a temporal desynchronization in the recovery of body composition, with complete recovery of fat mass preceeding that of lean mass. Under these conditions, persistent hyperphagia driven by the need to complete the recovery of lean tissue will result in the excess fat deposition (hence collateral fattening) and fat overshooting. After reviewing the main lines of evidence for the phenomenon of collateral fattening in body composition autoregulation, this article discusses the causes and determinants of the desynchronization in fat and lean tissue recovery leading to collateral fattening and fat overshooting, and points to their significance in the mechanisms by which dieting, developmental programming and sedentariness predispose to obesity

Relationship between fibroblastic foci profusion and high resolution CT morphology in fibrotic lung disease

Background Fibroblastic foci profusion on histopathology and severity of traction bronchiectasis on highresolution computed tomography (HRCT) have been shown to be predictors of mortality in patients with idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate the relationship between fibroblastic foci (FF) profusion and HRCT patterns in patients with a histopathologic diagnosis of usual interstitial pneumonia (UIP), fibrotic non-specific interstitial pneumonia (NSIP) and chronic hypersensitivity pneumonitis (CHP). Methods The HRCT scans of 162 patients with a histopathologic diagnosis of UIP or fibrotic NSIP (n = 162) were scored on extent of groundglass opacification, reticulation, honeycombing, emphysema and severity of traction bronchiectasis. For each patient, a fibroblastic foci profusion score based on histopathologic appearances was assigned. Relationships between extent of fibroblastic foci and individual HRCT patterns were investigated using univariate correlation analysis and multivariate linear regression. Results Increasing extent of reticulation (P < 0.0001) and increasing severity of traction bronchiectasis (P < 0.0001) were independently associated with increasing FF score within the entire cohort. Within individual multidisciplinary team diagnosis subgroups, the only significant independent association with FF score was severity of traction bronchiectasis in patients with idiopathic pulmonary fibrosis (IPF)/UIP (n = 66, r2 = 0.19, P < 0.0001) and patients with chronic hypersensitivity pneumonitis (CHP) (n = 49, r2 = 0.45, P < 0.0001). Furthermore, FF score had the strongest association with severity of traction bronchiectasis in patients with IPF (r2 = 0.34, P < 0.0001) and CHP (r2 = 0.35, P < 0.0001). There was no correlation between FF score and severity of traction bronchiectasis in patients with fibrotic NSIP. Global disease extent had the strongest association with severity of traction bronchiectasis in patients with fibrotic NSIP (r2 = 0.58, P < 0.0001). Conclusion In patients with fibrotic lung disease, profusion of fibroblastic foci is strikingly related to the severity of traction bronchiectasis, particularly in IPF and CHP. This may explain the growing evidence that traction bronchiectasis is a predictor of mortality in several fibrotic lung diseases

A Critical Role for Purinergic Signalling in the Mechanisms Underlying Generation of BOLD fMRI Responses

The mechanisms of neurovascular coupling underlying generation of BOLD fMRI signals remain incompletely understood. It has been proposed that release of vasoactive substances by astrocytes couples neuronal activity to changes in cerebrovascular blood flow. However, the role of astrocytes in fMRI responses remains controversial. Astrocytes communicate via release of ATP, and here we tested the hypothesis that purinergic signaling plays a role in the mechanisms underlying fMRI. An established fMRI paradigm was used to trigger BOLD responses in the forepaw region of the somatosensory cortex (SSFP) of an anesthetized rat. Forepaw stimulation induced release of ATP in the SSFP region. To interfere with purinergic signaling by promoting rapid breakdown of the vesicular and/or released ATP, a lentiviral vector was used to express a potent ectonucleotidase, transmembrane prostatic acid phosphatase (TMPAP), in the SSFP region. TMPAP expression had no effect on resting cerebral blood flow, cerebrovascular reactivity, and neuronal responses to sensory stimulation. However, TMPAP catalytic activity markedly reduced the magnitude of BOLD fMRI responses triggered in the SSFP region by forepaw stimulation. Facilitated ATP breakdown could result in accumulation of adenosine. However, blockade of A1 receptors had no effect on BOLD responses and did not reverse the effect of TMPAP. These results suggest that purinergic signaling plays a significant role in generation of BOLD fMRI signals. We hypothesize that astrocytes activated during periods of enhanced neuronal activity release ATP, which propagates astrocytic activation, stimulates release of vasoactive substances and dilation of cerebral vasculature

Optimal search strategies for identifying sound clinical prediction studies in EMBASE

BACKGROUND: Clinical prediction guides assist clinicians by pointing to specific elements of the patient's clinical presentation that should be considered when forming a diagnosis, prognosis or judgment regarding treatment outcome. The numbers of validated clinical prediction guides are growing in the medical literature, but their retrieval from large biomedical databases remains problematic and this presents a barrier to their uptake in medical practice. We undertook the systematic development of search strategies ("hedges") for retrieval of empirically tested clinical prediction guides from EMBASE. METHODS: An analytic survey was conducted, testing the retrieval performance of search strategies run in EMBASE against the gold standard of hand searching, using a sample of all 27,769 articles identified in 55 journals for the 2000 publishing year. All articles were categorized as original studies, review articles, general papers, or case reports. The original and review articles were then tagged as 'pass' or 'fail' for methodologic rigor in the areas of clinical prediction guides and other clinical topics. Search terms that depicted clinical prediction guides were selected from a pool of index terms and text words gathered in house and through request to clinicians, librarians and professional searchers. A total of 36,232 search strategies composed of single and multiple term phrases were trialed for retrieval of clinical prediction studies. The sensitivity, specificity, precision, and accuracy of search strategies were calculated to identify which were the best. RESULTS: 163 clinical prediction studies were identified, of which 69 (42.3%) passed criteria for scientific merit. A 3-term strategy optimized sensitivity at 91.3% and specificity at 90.2%. Higher sensitivity (97.1%) was reached with a different 3-term strategy, but with a 16% drop in specificity. The best measure of specificity (98.8%) was found in a 2-term strategy, but with a considerable fall in sensitivity to 60.9%. All single term strategies performed less well than 2- and 3-term strategies. CONCLUSION: The retrieval of sound clinical prediction studies from EMBASE is supported by several search strategies

SN 2005hj: Evidence for Two Classes of Normal-Bright SNe Ia and Implications for Cosmology

HET Optical spectra covering the evolution from about 6 days before to about 5 weeks after maximum light and the ROTSE-IIIb unfiltered light curve of the "Branch-normal" Type Ia Supernova SN 2005hj are presented. The host galaxy shows HII region lines at redshift of z=0.0574, which puts the peak unfiltered absolute magnitude at a somewhat over-luminous -19.6. The spectra show weak and narrow SiII lines, and for a period of at least 10 days beginning around maximum light these profiles do not change in width or depth and they indicate a constant expansion velocity of ~10,600 km/s. We analyzed the observations based on detailed radiation dynamical models in the literature. Whereas delayed detonation and deflagration models have been used to explain the majority of SNe Ia, they do not predict a long velocity plateau in the SiII minimum with an unvarying line profile. Pulsating delayed detonations and merger scenarios form shell-like density structures with properties mostly related to the mass of the shell, M_shell, and we discuss how these models may explain the observed SiII line evolution; however, these models are based on spherical calculations and other possibilities may exist. SN 2005hj is consistent with respect to the onset, duration, and velocity of the plateau, the peak luminosity and, within the uncertainties, with the intrinsic colors for models with M_shell=0.2 M_sun. Our analysis suggests a distinct class of events hidden within the Branch-normal SNe Ia. If the predicted relations between observables are confirmed, they may provide a way to separate these two groups. We discuss the implications of two distinct progenitor classes on cosmological studies employing SNe Ia, including possible differences in the peak luminosity to light curve width relation.Comment: ApJ accepted, 31 page

A sense of embodiment is reflected in people's signature size

BACKGROUND: The size of a person's signature may reveal implicit information about how the self is perceived although this has not been closely examined. METHODS/RESULTS: We conducted three experiments to test whether increases in signature size can be induced. Specifically, the aim of these experiments was to test whether changes in signature size reflect a person's current implicit sense of embodiment. Experiment 1 showed that an implicit affect task (positive subliminal evaluative conditioning) led to increases in signature size relative to an affectively neutral task, showing that implicit affective cues alter signature size. Experiments 2 and 3 demonstrated increases in signature size following experiential self-focus on sensory and affective stimuli relative to both conceptual self-focus and external (non-self-focus) in both healthy participants and patients with anorexia nervosa, a disorder associated with self-evaluation and a sense of disembodiment. In all three experiments, increases in signature size were unrelated to changes in self-reported mood and larger than manipulation unrelated variations. CONCLUSIONS: Together, these findings suggest that a person's sense of embodiment is reflected in their signature size

Pathways for outpatient management of venous thromboembolism in a UK centre.

It has become widely recognised that outpatient treatment may be suitable for many patients with venous thromboembolism. In addition, non-vitamin K antagonist oral anticoagulants that have been approved over the last few years have the potential to be an integral component of the outpatient care pathway, owing to their oral route of administration, lack of requirement for routine anticoagulation monitoring and simple dosing regimens. A robust pathway for outpatient care is also vital; one such pathway has been developed at Sheffield Teaching Hospitals in the UK. This paper describes the pathway and the arguments in its favour as an example of best practice and value offered to patients with venous thromboembolism. The pathway has two branches (one for deep vein thrombosis and one for pulmonary embolism), each with the same five-step process for outpatient treatment. Both begin from the point that the patient presents (in the Emergency Department, Thrombosis Clinic or general practitioner's office), followed by diagnosis, risk stratification, treatment choice and, finally, follow-up. The advantages of these pathways are that they offer clear, evidence-based guidance for the identification, diagnosis and treatment of patients who can safely be treated in the outpatient setting, and provide a detailed, stepwise process that can be easily adapted to suit the needs of other institutions. The approach is likely to result in both healthcare and economic benefits, including increased patient satisfaction and shorter hospital stays

Discovery of a Supernova Explosion at Half the Age of the Universe and its Cosmological Implications

The ultimate fate of the universe, infinite expansion or a big crunch, can be determined by measuring the redshifts, apparent brightnesses, and intrinsic luminosities of very distant supernovae. Recent developments have provided tools that make such a program practicable: (1) Studies of relatively nearby Type Ia supernovae (SNe Ia) have shown that their intrinsic luminosities can be accurately determined; (2) New research techniques have made it possible to schedule the discovery and follow-up observations of distant supernovae, producing well over 50 very distant (z = 0.3 -- 0.7) SNe Ia to date. These distant supernovae provide a record of changes in the expansion rate over the past several billion years. By making precise measurements of supernovae at still greater distances, and thus extending this expansion history back far enough in time, we can distinguish the slowing caused by the gravitational attraction of the universe's mass density Omega_M from the effect of a possibly inflationary pressure caused by a cosmological constant Lambda. We report here the first such measurements, with our discovery of a Type Ia supernova (SN 1997ap) at z = 0.83. Measurements at the Keck II 10-m telescope make this the most distant spectroscopically confirmed supernova. Over two months of photometry of SN 1997ap with the Hubble Space Telescope and ground-based telescopes, when combined with previous measurements of nearer SNe Ia, suggests that we may live in a low mass-density universe. Further supernovae at comparable distances are currently scheduled for ground and space-based observations.Comment: 12 pages and 4 figures (figure 4 is repeated in color and black and white) Nature, scheduled for publication in the 1 January, 1998 issue. Also available at http://www-supernova.lbl.go