AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease

<p>Abstract</p> <p>Background</p> <p>The incidence and mortality of hepatocellular cancer (HCC) complicating alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD) is rising in western societies. Despite knowing the at risk populations for HCC development, the lack of sensitive and specific means of surveillance hampers disease detection at curable stages. The most widely used serum HCC marker is alpha-fetoprotein (AFP), while PIVKA-II, glypican-3 (GP3) and Squamous Cell Carcinoma Antigen -1 (SCCA-1) have been proposed as new biomarkers. Assessment of these HCC biomarkers has largely been performed in patients with viral hepatitis. We conducted a cross sectional study assessing the value of these serum proteins, as well a novel candidate biomarker -follistatin – in patients with HCC arising on a background of ALD or NAFLD.</p> <p>Methods</p> <p>Pre-treatment serum samples from 50 patients with HCC arising on a background of ALD (n = 31) or NAFLD (n = 19) were assessed by specific ELISA assay for PIVKAII, Glypican-3, SCCA-1 and Follistatin. Results were compared and contrasted with a control patient group with biopsy proven steatohepatitis-related cirrhosis (n = 41). The diagnostic accuracy of each of the candidate biomarkers was evaluated using receiver operating characteristic (ROC) curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI). Performance was compared to that of the established biomarker, AFP.</p> <p>Results</p> <p>Serum levels of all proteins were assessed by specific ELISA assays. GP3, SCCA-1 and follistatin had no HCC surveillance benefit in these patients. AFP and PIVKAII were superior to the other markers, particularly in combination.</p> <p>Conclusion</p> <p>We conclude that while novel means of surveillance are urgently required, the combination of AFP and PIVKAII for HCC is an improvement on AFP alone in ALD/NAFLD patients. Furthermore, our data in this homogenous subset of patients- particularly that confirming no role for SCCA-1 – suggests that the choice of optimal biomarkers for HCC surveillance may be determined by the aetiology of underlying chronic liver disease.</p

Which medical error to disclose to patients and by whom? Public preference and perceptions of norm and current practice

<p>Abstract</p> <p>Background</p> <p>Disclosure of near miss medical error (ME) and who should disclose ME to patients continue to be controversial. Further, available recommendations on disclosure of ME have emerged largely in Western culture; their suitability to Islamic/Arabic culture is not known.</p> <p>Methods</p> <p>We surveyed 902 individuals attending the outpatient's clinics of a tertiary care hospital in Saudi Arabia. Personal preference and perceptions of norm and current practice regarding which ME to be disclosed (5 options: don't disclose; disclose if associated with major, moderate, or minor harm; disclose near miss) and by whom (6 options: any employee, any physician, at-fault-physician, manager of at-fault-physician, medical director, or chief executive director) were explored.</p> <p>Results</p> <p>Mean (SD) age of respondents was 33.9 (10) year, 47% were males, 90% Saudis, 37% patients, 49% employed, and 61% with college or higher education. The percentage (95% confidence interval) of respondents who preferred to be informed of harmful ME, of near miss ME, or by at-fault physician were 60.0% (56.8 to 63.2), 35.5% (32.4 to 38.6), and 59.7% (56.5 to 63.0), respectively. Respectively, 68.2% (65.2 to 71.2) and 17.3% (14.7 to 19.8) believed that as currently practiced, harmful ME and near miss ME are disclosed, and 34.0% (30.7 to 37.4) that ME are disclosed by at-fault-physician. Distributions of perception of norm and preference were similar but significantly different from the distribution of perception of current practice (P < 0.001). In a forward stepwise regression analysis, older age, female gender, and being healthy predicted preference of disclosure of near miss ME, while younger age and male gender predicted preference of no-disclosure of ME. Female gender also predicted preferring disclosure by the at-fault-physician.</p> <p>Conclusions</p> <p>We conclude that: 1) there is a considerable diversity in preferences and perceptions of norm and current practice among respondents regarding which ME to be disclosed and by whom, 2) Distributions of preference and perception of norm were similar but significantly different from the distribution of perception of current practice, 3) most respondents preferred to be informed of ME and by at-fault physician, and 4) one third of respondents preferred to be informed of near-miss ME, with a higher percentage among females, older, and healthy individuals.</p

At What Stage of Neural Processing Does Cocaine Act to Boost Pursuit of Rewards?

Dopamine-containing neurons have been implicated in reward and decision making. One element of the supporting evidence is that cocaine, like other drugs that increase dopaminergic neurotransmission, powerfully potentiates reward seeking. We analyze this phenomenon from a novel perspective, introducing a new conceptual framework and new methodology for determining the stage(s) of neural processing at which drugs, lesions and physiological manipulations act to influence reward-seeking behavior. Cocaine strongly boosts the proclivity of rats to work for rewarding electrical brain stimulation. We show that the conventional conceptual framework and methods do not distinguish between three conflicting accounts of how the drug produces this effect: increased sensitivity of brain reward circuitry, increased gain, or decreased subjective reward costs. Sensitivity determines the stimulation strength required to produce a reward of a given intensity (a measure analogous to the KM of an enzyme) whereas gain determines the maximum intensity attainable (a measure analogous to the vmax of an enzyme-catalyzed reaction). To distinguish sensitivity changes from the other determinants, we measured and modeled reward seeking as a function of both stimulation strength and opportunity cost. The principal effect of cocaine was a two-fourfold increase in willingness to pay for the electrical reward, an effect consistent with increased gain or decreased subjective cost. This finding challenges the long-standing view that cocaine increases the sensitivity of brain reward circuitry. We discuss the implications of the results and the analytic approach for theories of how dopaminergic neurons and other diffuse modulatory brain systems contribute to reward pursuit, and we explore the implications of the conceptual framework for the study of natural rewards, drug reward, and mood

An ecological future for weed science to sustain crop production and the environment. A review

Sustainable strategies for managing weeds are critical to meeting agriculture's potential to feed the world's population while conserving the ecosystems and biodiversity on which we depend. The dominant paradigm of weed management in developed countries is currently founded on the two principal tools of herbicides and tillage to remove weeds. However, evidence of negative environmental impacts from both tools is growing, and herbicide resistance is increasingly prevalent. These challenges emerge from a lack of attention to how weeds interact with and are regulated by the agroecosystem as a whole. Novel technological tools proposed for weed control, such as new herbicides, gene editing, and seed destructors, do not address these systemic challenges and thus are unlikely to provide truly sustainable solutions. Combining multiple tools and techniques in an Integrated Weed Management strategy is a step forward, but many integrated strategies still remain overly reliant on too few tools. In contrast, advances in weed ecology are revealing a wealth of options to manage weedsat the agroecosystem levelthat, rather than aiming to eradicate weeds, act to regulate populations to limit their negative impacts while conserving diversity. Here, we review the current state of knowledge in weed ecology and identify how this can be translated into practical weed management. The major points are the following: (1) the diversity and type of crops, management actions and limiting resources can be manipulated to limit weed competitiveness while promoting weed diversity; (2) in contrast to technological tools, ecological approaches to weed management tend to be synergistic with other agroecosystem functions; and (3) there are many existing practices compatible with this approach that could be integrated into current systems, alongside new options to explore. Overall, this review demonstrates that integrating systems-level ecological thinking into agronomic decision-making offers the best route to achieving sustainable weed management

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Probing intramolecular interactions in arylselenides using a property descriptor based approach

Although a large volume of experimental evidence is available on the existence of intramolecular nonbonding interactions between chalcogen atoms in main group organometallic compounds, the primary focus has been on the contact distances involving the chalcogen atoms. The important class of intramolecular Se center dot center dot center dot X (where X is O, S, N) nonbonding interaction in a series of organoselenium compounds is quantified using a new scheme based on a molecular property descriptor. In the present study, we have employed the nucleus-independent chemical shift [NICS(0)] values, as a property descriptor to evaluate the strength of exocyclic nonbonding interactions in a series of aryl selenides. The ab initio MP2 as well as density functional theory methods have been used in conjunction with Dunning's cc-pVDZ basis set. The quantified values of Se center dot center dot center dot X nonbonding interactions are compared with other schemes based on thermochemical equations such as homodesmic and ortho-para methods. The changes in NICS(O) values at the aryl ring center are found to be sensitive to the strength of exocyclic Se center dot center dot center dot X interaction