Hepatocellular carcinoma: Review of disease and tumor biomarkers.

© The Author(s) 2016.Hepatocellular carcinoma (HCC) is a common malignancy and now the second commonest global cause of cancer death. HCC tumorigenesis is relatively silent and patients experience late symptomatic presentation. As the option for curative treatments is limited to early stage cancers, diagnosis in non-symptomatic individuals is crucial. International guidelines advise regular surveillance of high-risk populations but the current tools lack sufficient sensitivity for early stage tumors on the background of a cirrhotic nodular liver. A number of novel biomarkers have now been suggested in the literature, which may reinforce the current surveillance methods. In addition, recent metabonomic and proteomic discoveries have established specific metabolite expressions in HCC, according to Warburgs phenomenon of altered energy metabolism. With clinical validation, a simple and non-invasive test from the serum or urine may be performed to diagnose HCC, particularly benefiting low resource regions where the burden of HCC is highest

Proximal Average Approximated Incremental Gradient Method for Composite Penalty Regularized Empirical Risk Minimization *

Abstract Proximal average (PA) is an approximation technique proposed recently to handle nonsmooth composite regularizer in empirical risk minimization problem. For nonsmooth composite regularizer, it is often difficult to directly derive the corresponding proximal update when solving with popular proximal update. While traditional approaches resort to complex splitting methods like ADMM, proximal average provides an alternative, featuring the tractability of implementation and theoretical analysis. Nevertheless, compared to SDCA-ADMM and SAG-ADMM which are examples of ADMM-based methods achieving faster convergence rate and low per-iteration complexity, existing PA-based approaches either converge slowly (e.g. PA-ASGD) or suffer from high per-iteration cost (e.g. PA-APG). In this paper, we therefore propose a new PA-based algorithm called PA-SAGA, which is optimal in both convergence rate and per-iteration cost, by incorporating into incremental gradient-based framework

Satisfaction with the Use of Different Technologies for Insulin Delivery and Glucose Monitoring Among Adults with Long-Standing Type 1 Diabetes and Problematic Hypoglycemia: 2-Year Follow-Up in the HypoCOMPaSS Randomized Clinical Trial

Background In the HypoCOMPaSS trial, adults with long-standing type 1 diabetes and problematic hypoglycaemia were randomised to compare insulin pump (CSII) vs multiple daily injections (MDI) and real-time continuous glucose monitoring (RT-CGM) vs conventional self-monitoring (SMBG). Our aim was to investigate participants\u27 satisfaction with these technologies at 6-month RCT endpoint and at 2-year follow-up. Methods Participants completed the Insulin Treatment Satisfaction Questionnaire (ITSQ) subscales \u27device delivery\u27 and \u27hypoglycaemia control\u27; and Glucose Monitoring Experience Questionnaire (GME-Q), assessing \u27convenience\u27, \u27effectiveness\u27, \u27intrusiveness\u27 and \u27total satisfaction\u27. We assessed change over time and between group differences by insulin and monitoring modalities. Results Participants (N=96) were: 64% women, aged 49\ub112 years, diabetes duration 29\ub112 years. At 6 months, participants reported improvements compared to baseline (all p<0.001) in satisfaction with insulin \u27delivery device\u27 (r=0.39) and \u27hypoglycaemia control\u27 (r=0.52), and trends towards significance in perceived \u27effectiveness\u27 (r=0.42) and \u27intrusiveness\u27 (r=0.27) of monitoring device (but not \u27convenience\u27, p=0.139). All improvements were sustained at 2 years. At 6 months, the only difference between arms was that greater satisfaction with insulin \u27delivery device\u27 was reported in the CSII group compared to MDI (p<0.001, r=0.40). No between-group differences were observed at 2 years. Conclusions Overall, significant improvements in participant satisfaction with diabetes technologies were observed over the 6-month RCT, in all domains except \u27convenience\u27, maintained at 2 years. While HypoCOMPaSS demonstrated non-inferiority of SMBG versus CGM, and MDI versus CSII in terms of biomedical outcomes, detailed assessments confirm participants\u27 satisfaction with delivery device was greater in those allocated to CSII than MDI

Strange Attractors in Dissipative Nambu Mechanics : Classical and Quantum Aspects

We extend the framework of Nambu-Hamiltonian Mechanics to include dissipation in $R^{3}$ phase space. We demonstrate that it accommodates the phase space dynamics of low dimensional dissipative systems such as the much studied Lorenz and R\"{o}ssler Strange attractors, as well as the more recent constructions of Chen and Leipnik-Newton. The rotational, volume preserving part of the flow preserves in time a family of two intersecting surfaces, the so called {\em Nambu Hamiltonians}. They foliate the entire phase space and are, in turn, deformed in time by Dissipation which represents their irrotational part of the flow. It is given by the gradient of a scalar function and is responsible for the emergence of the Strange Attractors. Based on our recent work on Quantum Nambu Mechanics, we provide an explicit quantization of the Lorenz attractor through the introduction of Non-commutative phase space coordinates as Hermitian $N \times N$ matrices in $R^{3}$. They satisfy the commutation relations induced by one of the two Nambu Hamiltonians, the second one generating a unique time evolution. Dissipation is incorporated quantum mechanically in a self-consistent way having the correct classical limit without the introduction of external degrees of freedom. Due to its volume phase space contraction it violates the quantum commutation relations. We demonstrate that the Heisenberg-Nambu evolution equations for the Quantum Lorenz system give rise to an attracting ellipsoid in the $3 N^{2}$ dimensional phase space.Comment: 35 pages, 4 figures, LaTe

Lipocalin 2 is protective against E. coli pneumonia

<p>Abstract</p> <p>Background</p> <p>Lipocalin 2 is a bacteriostatic protein that binds the siderophore enterobactin, an iron-chelating molecule produced by <it>Escherichia coli </it>(<it>E. coli</it>) that is required for bacterial growth. Infection of the lungs by <it>E. coli </it>is rare despite a frequent exposure to this commensal bacterium. Lipocalin 2 is an effector molecule of the innate immune system and could therefore play a role in hindering growth of <it>E. coli </it>in the lungs.</p> <p>Methods</p> <p>Lipocalin 2 knock-out and wild type mice were infected with two strains of <it>E. coli</it>. The lungs were removed 48 hours post-infection and examined for lipocalin 2 and MMP9 (a myeloid marker protein) by immunohistochemical staining and western blotting. Bacterial numbers were assessed in the lungs of the mice at 2 and 5 days after infection and mortality of the mice was monitored over a five-day period. The effect of administering ferrichrome (an iron source that cannot be bound by lipocalin 2) along with E.coli was also examined.</p> <p>Results</p> <p>Intratracheal installation of <it>E. coli </it>in mice resulted in strong induction of lipocalin 2 expression in bronchial epithelium and alveolar type II pneumocytes. Migration of myeloid cells to the site of infection also contributed to an increased lipocalin 2 level in the lungs. Significant higher bacterial numbers were observed in the lungs of lipocalin 2 knock-out mice on days 2 and 5 after infection with <it>E. coli </it>(p < 0.05). In addition, a higher number of <it>E. coli </it>was found in the spleen of surviving lipocalin 2 knock-out mice on day 5 post-infection than in the corresponding wild-type mice (p < 0.05). The protective effect against <it>E. coli </it>infection in wild type mice could be counteracted by the siderophore ferrichrome, indicating that the protective effect of lipocalin 2 depends on its ability to sequester iron.</p> <p>Conclusions</p> <p>Lipocalin 2 is important for protection of airways against infection by <it>E. coli</it>.</p

Financial incentives for return of service in underserved areas: a systematic review

<p>Abstract</p> <p>Background</p> <p>In many geographic regions, both in developing and in developed countries, the number of health workers is insufficient to achieve population health goals. Financial incentives for return of service are intended to alleviate health worker shortages: A (future) health worker enters into a contract to work for a number of years in an underserved area in exchange for a financial pay-off.</p> <p>Methods</p> <p>We carried out systematic literature searches of PubMed, the Excerpta Medica database, the Cumulative Index to Nursing and Allied Health Literature, and the National Health Services Economic Evaluation Database for studies evaluating outcomes of financial-incentive programs published up to February 2009. To identify articles for review, we combined three search themes (health workers or students, underserved areas, and financial incentives). In the initial search, we identified 10,495 unique articles, 10,302 of which were excluded based on their titles or abstracts. We conducted full-text reviews of the remaining 193 articles and of 26 additional articles identified in reference lists or by colleagues. Forty-three articles were included in the final review. We extracted from these articles information on the financial-incentive programs (name, location, period of operation, objectives, target groups, definition of underserved area, financial incentives and obligation) and information on the individual studies (authors, publication dates, types of study outcomes, study design, sample criteria and sample size, data sources, outcome measures and study findings, conclusions, and methodological limitations). We reviewed program results (descriptions of recruitment, retention, and participant satisfaction), program effects (effectiveness in influencing health workers to provide care, to remain, and to be satisfied with work and personal life in underserved areas), and program impacts (effectiveness in influencing health systems and health outcomes).</p> <p>Results</p> <p>Of the 43 reviewed studies 34 investigated financial-incentive programs in the US. The remaining studies evaluated programs in Japan (five studies), Canada (two), New Zealand (one) and South Africa (one). The programs started between 1930 and 1998. We identified five different types of programs (service-requiring scholarships, educational loans with service requirements, service-option educational loans, loan repayment programs, and direct financial incentives). Financial incentives to serve for one year in an underserved area ranged from year-2000 United States dollars 1,358 to 28,470. All reviewed studies were observational. The random-effects estimate of the pooled proportion of all eligible program participants who had either fulfilled their obligation or were fulfilling it at the time of the study was 71% (95% confidence interval 60–80%). Seven studies compared retention in the <it>same </it>(underserved) area between program participants and non-participants. Six studies found that participants were less likely than non-participants to remain in the same area (five studies reported the difference to be statistically significant, while one study did not report a significance level); one study did not find a significant difference in retention in the same area. Thirteen studies compared provision of care or retention in <it>any </it>underserved area between participants and non-participants. Eleven studies found that participants were more likely to (continue to) practice in any underserved area (nine studies reported the difference to be statistically significant, while two studies did not provide the results of a significance test); two studies found that program participants were significantly less likely than non-participants to remain in any underserved area. Seven studies investigated the satisfaction of participants with their work and personal lives in underserved areas.</p> <p>Conclusion</p> <p>Financial-incentive programs for return of service are one of the few health policy interventions intended to improve the distribution of human resources for health on which substantial evidence exists. However, the majority of studies are from the US, and only one study reports findings from a developing country, limiting generalizability. The existing studies show that financial-incentive programs have placed substantial numbers of health workers in underserved areas and that program participants are more likely than non-participants to work in underserved areas in the long run, even though they are less likely to remain at the site of original placement. As none of the existing studies can fully rule out that the observed differences between participants and non-participants are due to selection effects, the evidence to date does not allow the inference that the programs have caused increases in the supply of health workers to underserved areas.</p

Causal hierarchy within the thalamo-cortical network in spike and wave discharges

Background: Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1. Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy. © 2009 Vaudano et al