Epigenetic Abnormalities of 11p15.5 Region in Beckwith-Wiedemann Syndrome - A Report of Eight Indian Cases

Indian Journal of Pediatrics - To report a phenotypic series of eight patients of Beckwith-Wiedemann Syndrome (BWS) with abnormalities of 11p15.5 region to highlight the spectrum of phenotypic...     

Improving research and policy interactions requires a better understanding of what works in different contexts

There is keen interest in many jurisdictions in finding ways to improve the way that research evidence informs policy. One possible mechanism for this is to embed academics within government agencies either as advisers or full staff members. Our commentary argues that, in addition to considering the role of academics in government as proposed by Glied and colleagues, we need to understand better how research and policy interactions function across policy sectors. We believe more comparative research is needed to understand if and why academics from certain disciplines are more likely to be recruited to work in some policy sectors rather than others. We caution against treating government as monolithic by advocating the same model for collaborative interaction between academics and government. Lastly, we contend that contextualized research is needed to illuminate important drivers of research and policy interactions before we can recommend what is likely to be more and less effective in different policy sectors.     

In vitro analysis of 'smear layer' on human dentine using ac-impedance spectroscopy

OBJECTIVE: To analyse smear layers on human dentine using ac-impedance spectroscopy. METHODS: Dentine samples were prepared from extracted, sound, third molars. Impedance measurements were carried out on dentine samples before and after etching. After measuring, samples were examined under scanning electron microscope (SEM) to correlate electrical measurements with structure. RESULTS: Marked differences in impedance before and after etching were demonstrated. SEM investigation showed that a smear layer overlies dentine surfaces before etching, but completely disappeared after etching, leaving open dentinal tubules. CONCLUSIONS: The clinical removal of smear layers is still subjective. This objective method, based on combined ac-impedance and admittance measurement in vitro, has the potential to allow development of standardised techniques and if developed further may be of use in vivo.     

The effect of a selective cyclooxygenase-2 inhibitor (celecoxib) on chronic periodontitis

BACKGROUND: Non-steroidal anti-inflammatory agents inhibit the production of cyclooxygenase (COX) products and can attenuate bone loss. In this double-masked, placebo-controlled, randomized clinical trial, the efficacy of celecoxib (COX-2 inhibitor) was evaluated in conjunction with scaling and root planing (SRP) in subjects with chronic periodontitis (CP). METHODS: A total of 131 subjects were randomized to receive SRP and either celecoxib (200 mg) or placebo every day for 6 months. Clinical outcomes were assessed every 3 months for 12 months as mean changes from baseline. Primary efficacy parameters included clinical attachment level (CAL) and probing depth (PD). Secondary outcomes included percentages of tooth sites with CAL loss or gain > or =2 mm, changes in bleeding on probing (BOP), plaque index, and mobility. Prior to analysis, tooth sites were grouped based on baseline PD as shallow (1 to 3 mm), moderate (4 to 6 mm), or deep (> or =7 mm). RESULTS: Mean PD reduction and CAL gain were greater in the celecoxib group, primarily in moderate and deep sites, throughout the study (PD: 3.84 mm versus 2.06 mm, P <0.001; CAL: 3.74 mm versus 1.43 mm, P <0.0001 for deep sites at 12 months). The celecoxib group also exhibited a greater percentage of sites with > or =2 mm CAL gain and fewer sites with > or =2 mm CAL loss. Both groups showed improved plaque control and BOP scores. Demographic, social, and behavioral factors did not affect treatment outcomes. CONCLUSIONS: Celecoxib can be an effective adjunctive treatment to SRP to reduce progressive attachment loss in subjects with CP. Its beneficiary effect persisted even at 6 months postadministration. However, given the increased cardiovascular risks associated with the use of this drug, close patient supervision and strict adherence to dosage and administration guidelines established by the Unites States Food and Drug Administration are of paramount importance.     

Irrational exuberance and neural crash warning signals during endogenous experimental market bubbles

Groups of humans routinely misassign value to complex future events, especially in settings involving the exchange of resources. If properly structured, experimental markets can act as excellent probes of human group-level valuation mechanisms during pathological overvaluations—price bubbles. The connection between the behavioral and neural underpinnings of such phenomena has been absent, in part due to a lack of enabling technology. We used a multisubject functional MRI paradigm to measure neural activity in human subjects participating in experimental asset markets in which endogenous price bubbles formed and crashed. Although many ideas exist about how and why such bubbles may form and how to identify them, our experiment provided a window on the connection between neural responses and behavioral acts (buying and selling) that created the bubbles. We show that aggregate neural activity in the nucleus accumbens (NAcc) tracks the price bubble and that NAcc activity aggregated within a market predicts future price changes and crashes. Furthermore, the lowest-earning subjects express a stronger tendency to buy as a function of measured NAcc activity. Conversely, we report a signal in the anterior insular cortex in the highest earners that precedes the impending price peak, is associated with a higher propensity to sell in high earners, and that may represent a neural early warning signal in these subjects. Such markets could be a model system to understand neural and behavior mechanisms in other settings where emergent group-level activity exhibits mistaken belief or valuation.Asset price bubbles are extended periods in which prices rise well above fundamental values. Identifying bubbles and predicting crashes from price data alone is a notoriously difficult problem (1). However, prices are created by the collective behavior of the market participants, so neural activity could offer biomarkers for the evolution of price bubbles. Studies of asset price bubbles indicate a role for psychological factors such as “euphoria” (2), “irrational exuberance” (3), “mania” (4), “animal spirits” (5), and “sentiment” (6). We sought neural data supporting such psychological constructs that might help to identify price bubbles.We observed the formation and crash of endogenous bubbles in experimental asset markets (7, 8) using multisubject neuroimaging. In each of 16 market sessions, consisting of an average of 20 traders (range, 11–23), we measured the neural activity of 2–3 participants (n = 44 total) using functional magnetic resonance imaging (fMRI). Our market design is based upon ref. 9. Traders could buy or sell one risky asset unit in each period. Fig. 1A illustrates the sequence of experimental events. Each market had 50 trading periods. All subjects began with 100 units of experimental currency (a risk-free asset) and 6 units of a risky asset. Each period, the risky asset paid a currency dividend d of either 0.40 or 1.00 per unit (with equal probability), creating an expected dividend E[d] = 0.70. Currency earned a fixed interest rate r of 5% each period. After all 50 rounds of trading were completed, the risky asset was redeemed for 14 units of the risk-free currency.Open in a separate windowFig. 1.Asset market experiment. (A) Each period subjects viewed the following screens, in order: Positions, Order Entry (×5), Trading Results, and Dividends and Interest. (B) Order elicitation procedure. Subjects responded Buy, Sell, or Hold to a random (uniform) price draw from each of five bins, each of width equal to 10% of the last period’s price. The middle bin was centered on the last period’s price. (C) How the price is chosen (=market clearing). The highest price at which subjects responded Buy, and the lowest price at which subjects responded Sell, were entered into a closed book call market. Prices and trading outcomes were reported on the Trading Results screen.These parameters defined an unambiguous fundamental value for the risky asset. Buying the risky asset in period t at price P_t and selling it one period later leads to the expected net gain E_t[P_t+1] ? P_t? + ?E[d]. The same investment of P_t in the risk-free asset yields a sure net gain of rP_t. If these two amounts are equal—in economic terms, if asset prices are “in equilibrium”—then there is a stationary price equal to a constant fundamental value F defined by F = E[d]/r = 0.70/0.05 = 14. Prices persistently above F = 14 indicate a bubble; such a clear bubble measure is rarely available in field data. Fig. 2A illustrates the price paths for all 16 markets in this experiment. Bubbles are typical and large: the median price peak was 64.30 (range, 19.68–156.01). The bubble paths always result in a crash, and prices in the final period are near the fundamental F = 14 (median, 14.13). Fig. 2B illustrates a typical experimental session. This market bubble crashed after period 30. Trading volume is substantial, which means that prices do not result from a few extreme traders.Open in a separate windowFig. 2.Endogenous market bubbles. (A) Price paths in16 different experimental market sessions. The dark line shows the average price in each period over the 16 sessions. Plotted below the prices is the normalized per-subject volume for each period; error bars are SEs. (B) Single-session prices (Top) and trading volume (Middle) from one statistically typical experimental session. At Bottom is shown the risky asset holdings; each subject is indicated by a different color. MRI subjects are shown with thicker lines. The dashed line is the “clairvoyant” profit-maximizing share path (assuming subjects could somehow correctly anticipate all future prices).     

The role of stress in the mosaic of autoimmunity: An overlooked association

Stress is defined as the pscyophysiological reaction in which the steady state is disturbed or threatened. Stress is not always perceived as a negative response. Stress results when environmental demands exceed an individuals' adaptive capacities. Autoimmune diseases are heterogeneous group of chronic diseases which occur secondary to loss of self antigen tolerance. The etiopathogenesis of autoimmune disease is uncertain. Genetic factors as well as environmental factors appear to interplay, leading to a cascade of events resulting in disease onset. Stress has been postulated to play a role in disease onset in the genetically susceptible patients. During the stress response, catecholamines and glucocorticoids are released from locus coeruleus and adrenal gland. These biomolecules exert control over various immune cells in the innate and adaptive arms of the immune system, thereby altering the cytokine profile released. The increase of IL-4 promotes T-helper 2 (T_h2) cell differentiation, while the decrease in IL-12 and the increased IL-10 production reduce the number of T-helper 1 (T_h1) cells. The relationship between stress and autoimmune diseases is intricate. Stress has been shown to be associated with disease onset, and disease exacerbations in rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, Graves' disease as well as other autoimmune conditions. In certain conditions such as psoriasis, stress has been implicated in delaying lesion clearance upon the application of standard treatment regimes. Finally, psychological therapy and cognitive behavioral therapy aimed to reduce stress levels was shown to be effective in influencing better outcomes in many autoimmune diseases. The purpose of this paper is to closer inspect the clinical evidence regarding the role of stress on influencing the various aspects of disease entities.