MicroRNA in human cancer and chronic inflammatory diseases

MicroRNAs (miRNAs) are the non-coding RNAs that act as post-translational regulators to their complimentary messenger RNAs (mRNA). Due to their specific gene silencing property, miRNAs have been implicated in a number of cellular and developmental processes. Also, it has been proposed that a particular set of miRNA spectrum is expressed only in a particular type of tissue. Many interesting findings related to the differential expression of miRNAs in various human diseases including several types of cancers, neurodegenerative diseases and metabolic diseases have been reported. Deregulation of miRNA expression in different types of human diseases and the roles various miRNAs play as tumour suppressors as well as oncogenes, suggest their contribution to cancer and/or in other disease development. These findings have possible implications in the development of diagnostics and/or therapeutics in human malignancies. In this review, we discuss various miRNAs that are differentially expressed in human chronic inflammatory diseases, neurodegenerative diseases, cancer and the further prospective development of miRNA based diagnostics and therapeutics.

Surveillance of wild birds for avian influenza virus

Recent demand for increased understanding of avian influenza virus in its natural hosts, together with the development of high-throughput diagnostics, has heralded a new era in wildlife disease surveillance. However, survey design, sampling, and interpretation in the context of host populations still present major challenges. We critically reviewed current surveillance to distill a series of considerations pertinent to avian influenza virus surveillance in wild birds, including consideration of what, when, where, and how many to sample in the context of survey objectives. Recognizing that wildlife disease surveillance is logistically and financially constrained, we discuss pragmatic alternatives for achieving probability-based sampling schemes that capture this host-pathogen system. We recommend hypothesis-driven surveillance through standardized, local surveys that are, in turn, strategically compiled over broad geographic areas. Rethinking the use of existing surveillance infrastructure can thereby greatly enhance our global understanding of avian influenza and other zoonotic diseases.

Apoptosis goes on a chip : advances in the microfluidic analysis of programmed cell death

Recent years have brought enormous progress in cell-based lab-on-a-chip technologies, allowing dynamic studies of cell death with an unprecedented accuracy. As interest in the microfabricated technologies for cell-based bioassays is rapidly gaining momentum, we highlight the most promising technologies that provide a new outlook for the rapid assessment of programmed and accidental cell death and are applicable in drug discovery, high-content drug screening, and personalized clinical diagnostics.

Preserving the environment and traditional communities : a land use change modeling approach

Human populations can cause serious damage to the natural environment. This, however, depends on the type of society and its size. Many traditional communities have a balanced relation with the environment, using practices for managing the soil, water and natural resources in order to satisfy their needs that are compatible to the general goals of environmental preservation.

The most usual approach to environmental conservation in the world sees human beings as intruders, potentially destroyers of the nature and, as a consequence, generally requires local population to be expelled from the protected regions. This situation has generated social conflicts because many protected areas, particularly in developing countries, are inhabited by indigenous or other traditional communities.

The disagreement about expelling or maintaining traditional communities in environmental conservation areas is strengthened by the lack of diagnostics on which changes are produced or suffered by communities in the region where they live. This paper presents a methodology developed to analyse land use dynamics in region with environmental conservation and traditional communities. We seek a better understanding of the way traditional communities use their space, the spatial pattern of land uses, which factors drive land use change, which impacts can be seen in those regions and identify the effects of conservation policies on land use dynamics.

The application of the method to the National Park of Superagui, Brazil, has successfully performed characterisation, analysis and simulation of land use dynamics in a region of environmental importance. Testing different scenarios has suggested that the adoption of a less restrictive policy for environmental conservation would have resulted in less social conflict with the same environmental efficiency than the established current policy.

Overreporting of vitamin D deficiency by the Roche Elecsys vitamin D3 (25-OH) method

Background: Vitamin D deficiency is common. Recently Roche Diagnostics removed their Elecsys Vitamin D3 (25OH) electrochemiluminescence immunoassay (ECLIA) from use, citing deteriorating traceability to the reference method (liquid chromatography tandem mass spectrometry; LCMSMS). We investigated the performance of the Roche assay (2 assay formulations) against an LCMSMS method and the widely used DiaSorin radioimmunoassay (RIA) method.

Methods: Two sets of samples from separate populations were assayed for vitamin D. The first set was assayed using three different methods: RIA (DiaSorin) in 2004, polyclonal ECLIA (Roche) in early 2009 and LCMSMS in early 2010. The second set was assayed using polyclonal and monoclonal ECLIA (Roche) and LCMSMS in mid-2010.

Results: The correlation of the polyclonal ECLIA with the RIA was poor (ECLIA = 0.45 x RIA + 19, r² = 0.59, n = 773). LCMSMS results correlated with RIA (RIA = 0.86 x LCMSMS + 4, r² = 0.69, n = 49) better than with polyclonal ECLIA (polyclonal ECLIA = 0.55 x LCMSMS + 6, r² = 0.62, n = 55) despite a storage interval of 6 years.

In recently collected samples monoclonal and polyclonal immunoassays gave similar results (monoclonal ECLIA = 0.93 polyclonal ECLIA -3, r² = 0.60, n = 153). The correlation between monoclonal Roche ECLIA and LCMSMS in these samples was very poor (monoclonal ECLIA = 0.31 x LCMSMS + 23, r² = 0.27).

Conclusions: At the time of its removal from the market, the Roche Elecsys Vitamin D3 (25OH) assay showed unacceptable performance, underestimating vitamin D levels. It seems that this bias preceded the introduction of the monoclonal assay. The worldwide distribution of the assay and the duration of this bias likely led to a significant number of patients starting supplementation unnecessarily.

Robust-diagnostic regression : a prelude for inducing reliable knowledge from regression

Regression lies heart in statistics, it is the one of the most important branch of multivariate techniques available for extracting knowledge in almost every field of study and research. Nowadays, it has drawn a huge interest to perform the tasks with different fields like machine learning, pattern recognition and data mining. Investigating outlier (exceptional) is a century long problem to the data analyst and researchers. Blind application of data could have dangerous consequences and leading to discovery of meaningless patterns and carrying to the imperfect knowledge. As a result of digital revolution and the growth of the Internet and Intranet data continues to be accumulated at an exponential rate and thereby importance of detecting outliers and study their costs and benefits as a tool for reliable knowledge discovery claims perfect attention. Investigating outliers in regression has been paid great value for the last few decades within two frames of thoughts in the name of robust regression and regression diagnostics. Robust regression first wants to fit a regression to the majority of the data and then to discover outliers as those points that possess large residuals from the robust output whereas in regression diagnostics one first finds the outliers, delete/correct them and then fit the regular data by classical (usual) methods. At the beginning there seems to be much confusion but now the researchers reach to the consensus, robustness and diagnostics are two complementary approaches to the analysis of data and any one is not good enough. In this chapter, we discuss both of them under the unique spectrum of regression diagnostics. Chapter expresses the necessity and views of regression diagnostics as well as presents several contemporary methods through numerical examples in linear regression within each aforesaid category together with current challenges and possible future research directions. Our aim is to make the chapter self-explained maintaining its general accessibility.

Chimeric aptamers in cancer cell-targeted drug delivery

Aptamers are single-stranded structured oligonucleotides (DNA or RNA) that can bind to a wide range of targets ("apatopes") with high affinity and specificity. These nucleic acid ligands, generated from pools of random-sequence by an in vitro selection process referred to as systematic evolution of ligands by exponential enrichment (SELEX), have now been identified as excellent tools for chemical biology, therapeutic delivery, diagnosis, research, and monitoring therapy in real-time imaging. Today, aptamers represent an interesting class of modern pharmaceuticals which with their low immunogenic potential mimic extend many of the properties of monoclonal antibodies in diagnostics, research, and therapeutics. More recently, chimeric aptamer approach employing many different possible types of chimerization strategies has generated more stable and efficient chimeric aptamers with aptameraptamer, aptamernonaptamer biomacromolecules (siRNAs, proteins) and aptamernanoparticle chimeras. These chimeric aptamers when conjugated with various biomacromolecules like locked nucleic acid (LNA) to potentiate their stability, biodistribution, and targeting efficiency, have facilitated the accurate targeting in preclinical trials. We developed LNA-aptamer (anti-nucleolin and EpCAM) complexes which were loaded in iron-saturated bovine lactofeerin (Fe-blf)-coated dopamine modified surface of superparamagnetic iron oxide (Fe3O4) nanoparticles (SPIONs). This complex was used to deliver the specific aptamers in tumor cells in a co-culture model of normal and cancer cells. This review focuses on the chimeric aptamers, currently in development that are likely to find future practical applications in concert with other therapeutic molecules and modalities.

K-Complex Detection Using a Hybrid-Synergic Machine Learning Method

Sleep stage identification is the first step in modern sleep disorder diagnostics process. K-complex is an indicator for the sleep stage 2. However, due to the ambiguity of the translation of the medical standards into a computer-based procedure, reliability of automated K-complex detection from the EEG wave is still far from expectation. More specifically, there are some significant barriers to the research of automatic K-complex detection. First, there is no adequate description of K-complex that makes it difficult to develop automatic detection algorithm. Second, human experts only provided the label for whether a whole EEG segment contains K-complex or not, rather than individual labels for each subsegment. These barriers render most pattern recognition algorithms inapplicable in detecting K-complex. In this paper, we attempt to address these two challenges, by designing a new feature extraction method that can transform visual features of the EEG wave with any length into mathematical representation and proposing a hybrid-synergic machine learning method to build a K-complex classifier. The tenfold cross-validation results indicate that both the accuracy and the precision of this proposed model are at least as good as a human expert in K-complex detection.

Boron carbon nitride nanostructures from salt melts : tunable water-soluble phosphors

A simple, high yield, chemical process is developed to fabricate layered h-BN nanosheets and BCNO nanoparticles with a diameter of ca. 5 nm at 700 °C. The use of the eutectic LiCl/KCl salt melt medium enhances the kinetics of the reaction between sodium borohydride and urea or guanidine as well as the dispersion of the nanoparticles in water. The carbon content can be tuned from 0 to 50 mol % by adjusting the reactant ratio, thus providing precise control of the light emission of the particles in the range 440–528 nm while reaching a quantum yield of 26%. Because of their green synthesis, low toxicity, small size, and stability against aggregation in water, the as-obtained photoluminescent BCNO nanoparticles show promise for diagnostics and optoelectronics.

Propensity score matching and variations on the balancing test

Balancing tests are diagnostics designed for use with propensity score methods, a widely used non-experimental approach in the evaluation literature. Such tests provide useful information on whether plausible counterfactuals have been created. Currently, multiple balancing tests exist in the literature but it is unclear which is the most useful. This article highlights the poor size properties of commonly employed balancing tests and attempts to shed some light on the link between the results of balancing tests and bias of the evaluation estimator. The simulation results suggest that in scenarios where the conditional independence assumption holds, a permutation version of the balancing test described in Dehejia and Wahba (Rev Econ Stat 84:151–161, 2002) can be useful in applied study. The proposed test has good size properties. In addition, the test appears to have good power for detecting a misspecification in the link function and some power for detecting an omission of relevant non-linear terms involving variables that are included at a lower order.

Surface-scribed transparency-based microplates

Transparency sheets, which are normally associated with use on overhead projectors, offer lowered costs and high amenability for optical diagnostics in microplate instrumentation. An alternative microplate design in which circles are scribed on the surface of the transparency to create the boundaries to hold the drop in place is investigated here. The 3D profile of the scribed regions obtained optically showed strong likelihood of affecting three-phase contact line interactions. During dispensation, the contact angle (?95°) was larger than the drop advancing state (?80°) due to a period of nonadhesion, where the contact angle later reduced to the drop advancing state followed by increase in the liquid area coverage on the substrate. It was established that 50 ?L was needed to fill the well fully, and the maximum volume retainable before breaching was 190 ?L. While the tilt angle needed for displacement reduced significantly from 50 to 95 ?L, this was markedly better than nonscribed surfaces, where tilt angles always had to be kept to within 30°. It was found that there was greater ability to fill the well with smaller volumes with dispensation at the center. This was attributed to the growing contact line not meeting the scribed edge in parallel if liquid was dispensed closer to it, wherein pinning reduction in some directions permitted liquid travel along the scribed edge to undergo contact angle hysteresis. Fluorescence measurements conducted showed no performance compromise when using scribed transparency microplates over standard microplates.

Aptamers as theranostic agents: modifications, serum stability and functionalisation

Aptamers, and the selection process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX) used to generate them, were first described more than twenty years ago. Since then, there have been numerous modifications to the selectionprocedures. This review discusses the use of modified bases as a means of enhancing serum stability and producing effective therapeutic tools, as well as functionalising these nucleic acids to be used as potential diagnostic agents.

Impact of HIV-associated conditions on mortality in people commencing anti-retroviral therapy in resource limited settings

Objectives: To identify associations between specific WHO stage 3 and 4 conditions diagnosed after ART initiation and all cause mortality for patients in resource-limited settings (RLS).

Design, Setting: Analysis of routine program data collected prospectively from 25 programs in eight countries between 2002 and 2010.

Subjects, Participants: 36,664 study participants with median ART follow-up of 1.26 years (IQR 0.55–2.27).

Outcome Measures: Using a proportional hazards model we identified factors associated with mortality, including the occurrence of specific WHO clinical stage 3 and 4 conditions during the 6-months following ART initiation.

Results: There were 2922 deaths during follow-up (8.0%). The crude mortality rate was 5.41 deaths per 100 person-years (95% CI: 5.21–5.61). The diagnosis of any WHO stage 3 or 4 condition during the first 6 months of ART was associated with
increased mortality (HR: 2.21; 95% CI: 1.97–2.47). After adjustment for age, sex, region and pre-ART CD4 count, a diagnosis of extrapulmonary cryptococcosis (aHR: 3.54; 95% CI: 2.74–4.56), HIV wasting syndrome (aHR: 2.92; 95%CI: 2.21 -3.85), nontuberculous mycobacterial infection (aHR: 2.43; 95% CI: 1.80–3.28) and Pneumocystis pneumonia (aHR: 2.17; 95% CI 1.80–3.28) were associated with the greatest increased mortality. Cerebral toxoplasmosis, pulmonary and extra-pulmonary
tuberculosis, Kaposi’s sarcoma and oral and oesophageal candidiasis were associated with increased mortality, though at lower rates.

Conclusions: A diagnosis of certain WHO stage 3 and 4 conditions is associated with an increased risk of mortality in those initiating ART in RLS. This information will assist initiatives to reduce excess mortality, including prioritization of resources for
diagnostics, therapeutic interventions and research.