Risk Factors for Suicide Attempts Among Alcohol Dependent Patients

Suicidal behavior is a common and important problem among alcohol dependent patients. The study was designed to examine risk factors for attempting suicide in 499 alcohol dependent patients. Those who had attempted suicide (N = 198) were more likely to be female, report a family history of suicidal behavior, report more childhood trauma, report greater levels of aggressive behavior, began heavy drinking earlier, and were more likely to have received antidepressant medication. Logistic regression analysis showed that gender, family history, and childhood sexual abuse history made significant and independent contributions to the risk of a suicide attempt. Thus, developmental, personality, family history, social, and comorbidity risk factors may differentiate alcohol dependent patients who have attempted suicide from those who have not.     

Heterotopic Bone Formation About the Hip Undergoes Endochondral Ossification: A Rabbit Model

Background

Heterotopic ossification (HO) occurs most commonly after trauma and surgery about the hip and may compromise subsequent function. Currently available animal models describing the cellular progression of HO are based on exogenous osteogenic induction agents and may not reflect the processes following trauma.

Questions/purposes

We therefore sought to characterize the histologic progression of heterotopic bone formation in an animal model that recapitulates the human condition without the addition of exogenous osteogenic material.

Methods

We used a rabbit model that included intramedullary instrumentation of the upper femur and ischemic crush injury of the gluteal muscle. Bilateral surgical induction procedures were performed on 30 animals with the intention of inciting the process of HO; no supplemental osteogenic stimulants were used. Three animals were sacrificed at each of 10 predetermined times between 1 day and 26 weeks postoperatively and the progression of tissue maturation was graded histologically using a five-item scale.

Results

Heterotopic bone reliably formed de novo and consistently followed a pathway of endochondral ossification. Chondroid elements were found in juxtaposition with immature woven bone in all sections that contained mature osseous elements.

Conclusions

These results establish that HO occurs in an animal model mimicking the human condition following surgical trauma about the hip; it is predictable in its histologic progression and follows a pathway of endochondral bone formation.

Clinical Relevance

By showing a consistent pathway of endochondral ossification leading to ectopic bone formation, this study provides a basis for understanding the mechanisms by which HO might be mitigated by interventions.     

Myocardial migration by fibroblast progenitor cells is blood pressure dependent in a model of angII myocardial fibrosis

Activation of the renin-angiotensin system (RAS) is thought to promote myocardial fibrosis. However, it is unclear whether this physiological fibrotic response results from chronic hemodynamic stress or from direct cellular signaling. Male C57B/6 mice were randomly assigned to receive angiotensin II (AngII) (2.0?μg?kg(-1)?min(-1)), AngII+hydralazine (6.9?μg?kg(-1)?min(-1)) or saline (control) via osmotic pumps for 7 days. Blood pressure was measured via noninvasive plethysmography. Hearts were harvested and processed for analysis. Cellular infiltration and collagen deposition were analyzed using histological staining. Molecular mediators were assessed using quantitative RT-PCR. As previously described, animals that received AngII developed hypertension and multifocal cellular infiltration by SMA(+)/CD133(+) fibroblast progenitors followed by collagen deposition. The coadministration of hydralazine with AngII completely inhibited the hypertensive effects of AngII (P0.01) and resulted in minimal cellular infiltration and minimal collagen deposition. These findings were in the context of persistent RAS activation, which was evidenced by elevation in serum aldosterone levels in animals that received AngII or AngII+hydralazine compared with animals that received saline. At the molecular level, infusion of AngII resulted in the significant upregulation of profibrotic factors (connective tissue growth factor-7.8±0.7 fold), proinflammatory mediators (TNFα-4.6±0.8 fold; IL-1β-6.4±2.6 fold) and chemokines (CCL2-3.8±1.0 fold; CXCL12-3.2±0.4 fold), which were inhibited when hydralazine was also infused. We provide evidence that myocardial infiltration by fibroblast progenitor cells secondary to AngII and the resultant fibrosis can be prevented by the addition of hydralazine. Furthermore, the beneficial effects of hydralazine were observed while maintaining RAS activation, suggesting that the mechanism of fibrosis is blood pressure dependent.     

Navigating Uncertainty in the Management of Incidental Findings

The lack of prospective outcomes studies for many types of incidental findings limits our understanding of both their natural history and the potential efficacy of treatment. To support decision making for the management of incidental findings, major sources of uncertainty in management pathways can be mapped and analyzed using mathematical models. This process yields important insights into how uncertainty influences the best treatment decision. Here, we consider a classification scheme, grounded in decision science, which exposes various levels and types of uncertainty in the management of incidental findings and addresses (1) disease-related risks, which are considered in context of a patient’s competing causes of mortality; (2) potential degrees of intervention; (3) strength of evidence; and (4) patients’ treatment-related preferences. Herein we describe how categorizing uncertainty by the sources, issues, and locus can build a framework from which to improve the management of incidental findings. Accurate and comprehensive handling of uncertainty will improve the quality of related decision making and will help guide future research priorities.     

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.     

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 science and application of IPS e.Max dental ceramic

The aim of this paper is to report the state of current literature and recommendations for the lithium disilicate glass-ceramic IPS e.Max. The materials science, mechanical and optical properties were reviewed. Additionally an assessment was conducted of current implementation recommendations and clinical outcomes. This paper provides a brief historical overview, summary of the findings the findings of current literature, and clinical recommendation for the use of IPS e.Max CAD in dental applications.