Refining the role of laparoscopy and laparoscopic ultrasound in the staging of presumed pancreatic head and ampullary tumours

Laparoscopy and laparoscopic ultrasound have been validated previously as staging tools for pancreatic cancer. The aim of this study was to identify if assessment of vascular involvement with abdominal computed tomography (CT) would allow refinement of the selection criteria for laparoscopy and laparoscopic ultrasound (LUS). The details of patients staged with LUS and abdominal CT were obtained from the unit's pancreatic cancer database. A CT grade (O, A-F) of vascular involvement was recorded by a single radiologist. Of 152 patients, who underwent a LUS, 56 (37%) had unresectable disease. Three of 26 (12%) patients with CT grade O, 27 of 88 (31%) patients with CT grade A to D, 17 of 29 (59%) patients with CT grade E and all nine patients with CT grade F were found to have unresectable disease. In all, 24% of patients with tumours <3 cm were found to have unresectable disease. In those patients with tumours considered unresectable, local vascular involvement was found in 56% of patients and vascular involvement with metastatic disease in 17%, while 20% of patients had liver metastases alone and 5% had isolated peritoneal metastases. The remaining patient was deemed unfit for resection. Selective use of laparoscopic ultrasound is indicated in the staging of periampullary tumours with CT grades A to D

Cost-Effectiveness of Interventions to Prevent Disability in Leprosy: A Systematic Review

Background: Prevention of disability (POD) is one of the key objectives of leprosy programmes. Recently, coverage and access have been identified as the priority issues in POD. Assessing the cost-effectiveness of POD interventions is highly relevant to understanding the barriers and opportunities to achieving universal coverage and access with limited resources. The purpose of this study was to systematically review the quality of existing cost-effectiveness evidence and discuss implications for future research and strategies to prevent disability in leprosy and other disabling conditions. Methodology/Principal Findings: We searched electronic databases (NHS EED, MEDLINE, EMBASE, and LILACS) and databases of ongoing trials (www.controlled-trials.com/mrct/, www.who.int/trialsearch). We checked reference lists and contacted experts for further relevant studies. We included studies that reported both cost and effectiveness outcomes of two or more alternative interventions to prevent disability in leprosy. We assessed the quality of the identified studies using a standard checklist for critical appraisal of economic evaluations of health care programmes. We found 66 citations to potentially relevant studies and three met our criteria. Two were randomised controlled trials (footwear, management of neuritis) and one was a generic model-based study (cost per DALY). Generally, the studies were small in size, reported inadequately all relevant costs, uncertainties in estimates, and issues of concern and were based on limited data sources. No cost-effectiveness data on self-care, which is a key strategy in POD, was found. Conclusion/Significance: Evidence for cost-effectiveness of POD interventions for leprosy is scarce. High quality research is needed to identify POD interventions that offer value for money where resources are very scarce, and to develop strategies aimed at available, affordable and sustainable quality POD services for leprosy. The findings are relevant for other chronically disabling conditions, such as lymphatic filariasis, Buruli ulcer and diabetes in developing countries

Lipoglycans Contribute to Innate Immune Detection of Mycobacteria

Innate immune recognition is based on the detection, by pattern recognition receptors (PRRs), of molecular structures that are unique to microorganisms. Lipoglycans are macromolecules specific to the cell envelope of mycobacteria and related genera. They have been described to be ligands, as purified molecules, of several PRRs, including the C-type lectins Mannose Receptor and DC-SIGN, as well as TLR2. However, whether they are really sensed by these receptors in the context of a bacterium infection remains unclear. To address this question, we used the model organism Mycobacterium smegmatis to generate mutants altered for the production of lipoglycans. Since their biosynthesis cannot be fully abrogated, we manipulated the biosynthesis pathway of GDP-Mannose to obtain some strains with either augmented (∼1.7 fold) or reduced (∼2 fold) production of lipoglycans. Interestingly, infection experiments demonstrated a direct correlation between the amount of lipoglycans in the bacterial cell envelope on one hand and the magnitude of innate immune signaling in TLR2 reporter cells, monocyte/macrophage THP-1 cell line and human dendritic cells, as revealed by NF-κB activation and IL-8 production, on the other hand. These data establish that lipoglycans are bona fide Microbe-Associated Molecular Patterns contributing to innate immune detection of mycobacteria, via TLR2 among other PRRs

Variations in influenza vaccination coverage among the high-risk population in Sweden in 2003/4 and 2004/5: a population survey

<p>Abstract</p> <p>Background</p> <p>In Sweden, the vaccination campaign is the individual responsibility of the counties, which results in different arrangements. The aim of this study was to find out whether influenza vaccination coverage rates (VCRs) had increased between 2003/4 and 2004/5 among population at high risk and to find out the influence of personal preferences, demographic characteristics and health care system characteristics on VCRs.</p> <p>Methods</p> <p>An average sample of 2500 persons was interviewed each season (2003/4 and 2004/5). The respondents were asked whether they had had an influenza vaccination, whether they suffered from chronic conditions and the reasons of non-vaccination. For every county the relevant health care system characteristics were collected via a questionnaire sent to the medical officers of communicable diseases.</p> <p>Results</p> <p>No difference in VCR was found between the two seasons. Personal invitations strongly increased the chance of having had a vaccination. For the elderly, the number of different health care professionals in a region involved in administering vaccines decreased this chance.</p> <p>Conclusion</p> <p>Sweden remained below the WHO-recommendations for population at high risk due to disease. To meet the 2010 WHO-recommendation further action may be necessary to increase vaccine uptake. Increasing the number of personal invitations and restricting the number of different administrators responsible for vaccination may be effective in increasing VCRs among the elderly.</p

Circulating microRNAs as novel biomarkers for diabetes mellitus.

Diabetes mellitus is characterized by insulin secretion from pancreatic β cells that is insufficient to maintain blood glucose homeostasis. Autoimmune destruction of β cells results in type 1 diabetes mellitus, whereas conditions that reduce insulin sensitivity and negatively affect β-cell activities result in type 2 diabetes mellitus. Without proper management, patients with diabetes mellitus develop serious complications that reduce their quality of life and life expectancy. Biomarkers for early detection of the disease and identification of individuals at risk of developing complications would greatly improve the care of these patients. Small non-coding RNAs called microRNAs (miRNAs) control gene expression and participate in many physiopathological processes. Hundreds of miRNAs are actively or passively released in the circulation and can be used to evaluate health status and disease progression. Both type 1 diabetes mellitus and type 2 diabetes mellitus are associated with distinct modifications in the profile of miRNAs in the blood, which are sometimes detectable several years before the disease manifests. Moreover, circulating levels of certain miRNAs seem to be predictive of long-term complications. Technical and scientific obstacles still exist that need to be overcome, but circulating miRNAs might soon become part of the diagnostic arsenal to identify individuals at risk of developing diabetes mellitus and its devastating complications

Design Constraints on a Synthetic Metabolism

A metabolism is a complex network of chemical reactions that converts sources of energy and chemical elements into biomass and other molecules. To design a metabolism from scratch and to implement it in a synthetic genome is almost within technological reach. Ideally, a synthetic metabolism should be able to synthesize a desired spectrum of molecules at a high rate, from multiple different nutrients, while using few chemical reactions, and producing little or no waste. Not all of these properties are achievable simultaneously. We here use a recently developed technique to create random metabolic networks with pre-specified properties to quantify trade-offs between these and other properties. We find that for every additional molecule to be synthesized a network needs on average three additional reactions. For every additional carbon source to be utilized, it needs on average two additional reactions. Networks able to synthesize 20 biomass molecules from each of 20 alternative sole carbon sources need to have at least 260 reactions. This number increases to 518 reactions for networks that can synthesize more than 60 molecules from each of 80 carbon sources. The maximally achievable rate of biosynthesis decreases by approximately 5 percent for every additional molecule to be synthesized. Biochemically related molecules can be synthesized at higher rates, because their synthesis produces less waste. Overall, the variables we study can explain 87 percent of variation in network size and 84 percent of the variation in synthesis rate. The constraints we identify prescribe broad boundary conditions that can help to guide synthetic metabolism design

Micropropagation and conservation of selected endangered anticancer medicinal plants from the Western Ghats of India

Globally, cancer is a constant battle which severely affects the human population. The major limitations of the anticancer drugs are the deleterious side effects on the quality of life. Plants play a vital role in curing many diseases with minimal or no side effects. Phytocompounds derived from various medicinal plants serve as the best source of drugs to treat cancer. The global demand for phytomedicines is mostly reached by the medicinal herbs from the tropical nations of the world even though many plant species are threatened with extinction. India is one of the mega diverse countries of the world due to its ecological habitats, latitudinal variation, and diverse climatic range. Western Ghats of India is one of the most important depositories of endemic herbs. It is found along the stretch of south western part of India and constitutes rain forest with more than 4000 diverse medicinal plant species. In recent times, many of these therapeutically valued herbs have become endangered and are being included under the red-listed plant category in this region. Due to a sharp rise in the demand for plant-based products, this rich collection is diminishing at an alarming rate that eventually triggered dangerous to biodiversity. Thus, conservation of the endangered medicinal plants has become a matter of importance. The conservation by using only in situ approaches may not be sufficient enough to safeguard such a huge bio-resource of endangered medicinal plants. Hence, the use of biotechnological methods would be vital to complement the ex vitro protection programs and help to reestablish endangered plant species. In this backdrop, the key tools of biotechnology that could assist plant conservation were developed in terms of in vitro regeneration, seed banking, DNA storage, pollen storage, germplasm storage, gene bank (field gene banking), tissue bank, and cryopreservation. In this chapter, an attempt has been made to critically review major endangered medicinal plants that possess anticancer compounds and their conservation aspects by integrating various biotechnological tool

Evaluation in artificial intelligence: From task-oriented to ability-oriented measurement

The final publication is available at Springer via http://dx.doi.org/ 10.1007/s10462-016-9505-7.The evaluation of artificial intelligence systems and components is crucial for the progress of the discipline. In this paper we describe and critically assess the different ways AI systems are evaluated, and the role of components and techniques in these systems. We first focus on the traditional task-oriented evaluation approach. We identify three kinds of evaluation: human discrimination, problem benchmarks and peer confrontation. We describe some of the limitations of the many evaluation schemes and competitions in these three categories, and follow the progression of some of these tests. We then focus on a less customary (and challenging) ability-oriented evaluation approach, where a system is characterised by its (cognitive) abilities, rather than by the tasks it is designed to solve. We discuss several possibilities: the adaptation of cognitive tests used for humans and animals, the development of tests derived from algorithmic information theory or more integrated approaches under the perspective of universal psychometrics. We analyse some evaluation tests from AI that are better positioned for an ability-oriented evaluation and discuss how their problems and limitations can possibly be addressed with some of the tools and ideas that appear within the paper. Finally, we enumerate a series of lessons learnt and generic guidelines to be used when an AI evaluation scheme is under consideration.I thank the organisers of the AEPIA Summer School On Artificial Intelligence, held in September 2014, for giving me the opportunity to give a lecture on 'AI Evaluation'. This paper was born out of and evolved through that lecture. The information about many benchmarks and competitions discussed in this paper have been contrasted with information from and discussions with many people: M. Bedia, A. Cangelosi, C. Dimitrakakis, I. GarcIa-Varea, Katja Hofmann, W. Langdon, E. Messina, S. Mueller, M. Siebers and C. Soares. Figure 4 is courtesy of F. Martinez-Plumed. Finally, I thank the anonymous reviewers, whose comments have helped to significantly improve the balance and coverage of the paper. This work has been partially supported by the EU (FEDER) and the Spanish MINECO under Grants TIN 2013-45732-C4-1-P, TIN 2015-69175-C4-1-R and by Generalitat Valenciana PROMETEOII2015/013.José Hernández-Orallo (2016). Evaluation in artificial intelligence: From task-oriented to ability-oriented measurement. 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