Corneal confocal microscopy detects early nerve regeneration in diabetic neuropathy after simultaneous pancreas and kidney transplantation

Diabetic neuropathy is associated with increased morbidity and mortality. To date, limited data in subjects with impaired glucose tolerance and diabetes demonstrate nerve fiber repair after intervention. This may reflect a lack of efficacy of the interventions but may also reflect difficulty of the tests currently deployed to adequately assess nerve fiber repair, particularly in short-term studies. Corneal confocal microscopy (CCM) represents a novel noninvasive means to quantify nerve fiber damage and repair. Fifteen type 1 diabetic patients undergoing simultaneous pancreas-kidney transplantation (SPK) underwent detailed assessment of neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy, corneal sensitivity, and CCM at baseline and at 6 and 12 months after successful SPK. At baseline, diabetic patients had a significant neuropathy compared with control subjects. After successful SPK there was no significant change in neurologic impairment, neurophysiology, QST, corneal sensitivity, and intraepidermal nerve fiber density (IENFD). However, CCM demonstrated significant improvements in corneal nerve fiber density, branch density, and length at 12 months. Normalization of glycemia after SPK shows no significant improvement in neuropathy assessed by the neurologic deficits, QST, electrophysiology, and IENFD. However, CCM shows a significant improvement in nerve morphology, providing a novel noninvasive means to establish early nerve repair that is missed by currently advocated assessment techniques.

Ten reasons why rigid contact lenses are obsolete

There have only been minor improvements in rigid lens material developments since silicone acrylates and fluoro-silicone acrylates were introduced over a quarter of a century ago. Although there have been enhancements in mechanical lathing technology in the rigid lens field - primarily as a result of developments in computer-controlled systems - rigid lenses are still manufactured using labour-intensive lathing processes, which is why the lens unit cost remains much higher than for disposable soft lenses.

Targeted therapies in non-small cell lung cancer

The majority of non-small cell lung cancer (NSCLC) patients present with advanced disease and with a 5 year survival rate of <15% for these patients, treatment outcomes are considered extremely disappointing. Standard chemotherapy regimens provide some improvement to ~40% of patients. However, intrinsic and acquired chemoresistance are a significant problem and hinder sustained long term benefits of such treatments. Advances in proteomic and genomic profiling have increased our understanding of the aberrant molecular mechanisms that are driving an individual's tumour. The increased sensitivity of these technologies has enabled molecular profiling at the stage of initial biopsy thus paving the way for a more personalised approach to the treatment of cancer patients. Improvements in diagnostics together with a wave of new targeted small molecule inhibitors and monoclonal antibodies have revolutionised the treatment of cancer. To date there are essentially three targeted agents approved for clinical use in NSCLC. The tyrosine kinase inhibitor (TKI) erlotinib, which targets the epidermal growth factor receptor (EGFR) TK domain, has proven to be an effective treatment strategy in patients who harbour activating mutations in the EGFR TK domain. Bevacizumab a monoclonal antibody targeting the vascular endothelial growth factor (VEGF) can improve survival, response rates, and progression-free survival when used in combination with chemotherapy. Crizotinib, a small-molecule drug, inhibits the tyrosine kinase activity of the echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) fusion protein, resulting in decreased tumour cell growth, migration, and invasiveness in patients with locally advanced or metastatic NSCLC. The clinical relevance of several other targeted agents are under investigation in distinct molecular subsets of patients with key "driver" mutations including: KRAS, HER2, BRAF, MET, PIK3CA, AKT1,MAP2K1, ROS1 and RET. Often several pathways are activated simultaneously and crosstalk between pathways allows tumour cells to escape the inhibition of a single targeted agent. This chapter will explore the clinical development of currently available targeted therapies for NSCLC as well as those in clinical trials and will examine the synergy between cytotoxic therapies.

Long non coding RNAs (lncRNAs) are dysregulated in Malignant Pleural Mesothelioma (MPM)

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanced stage and is characterized by a long latency period (20-40 years between initial exposure and diagnosis) and prior exposure to asbestos. Currently accurate diagnosis of MPM is difficult due to the lack of sensitive biomarkers and despite minor improvements in treatment, median survival rates do not exceed 12 months. Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) play an important functional role in cancer biology. LncRNAs are a class of recently discovered non-protein coding RNAs >200 nucleotides in length with a role in regulating transcription. Here we used NCode long noncoding microarrays to identify differentially expressed lncRNAs potentially involved in MPM pathogenesis. High priority candidate lncRNAs were selected on the basis of statistical (P<0.05) and biological significance (>3-fold difference). Expression levels of 9 candidate lncRNAs were technically validated using RT-qPCR, and biologically validated in three independent test sets: (1) 57 archived MPM tissues obtained from extrapleural pneumonectomy patients, (2) 15 cryopreserved MPM and 3 benign pleura, and (3) an extended panel of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of these lncRNAs in independent datasets. ROC curve analysis showed that two candidates were able to separate benign pleura and MPM with high sensitivity and specificity, and were associated with nodal metastases and survival following induction chemotherapy. These results suggest that lncRNAs have potential to serve as biomarkers in MPM.

Symptom control and quality of life in lux-lung 3 : a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations

Purpose Patient-reported symptoms and health-related quality of life (QoL) benefits were investigated in a randomized, phase III trial of afatinib or cisplatin/pemetrexed. Patients and Methods Three hundred forty-five patients with advanced epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma were randomly assigned 2:1 to afatinib 40 mg per day or up to six cycles of cisplatin/pemetrexed. Lung cancer symptoms and health-related QoL were assessed every 21 days until progression using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Lung Cancer-13 questionnaires. Analyses of cough, dyspnea, and pain were preplanned, including percentage of patients who improved on therapy, time to deterioration of symptoms, and change in symptoms over time. Results Questionnaire compliance was high. Compared with chemotherapy, afatinib significantly delayed the time to deterioration for cough (hazard ratio [HR], 0.60; 95% CI, 0.41 to 0.87; P = .007) and dyspnea (HR, 0.68; 95% CI, 0.50 to 0.93; P = .015), but not pain (HR, 0.83; 95% CI, 0.62 to 1.10; P = .19). More patients on afatinib (64%) versus chemotherapy (50%) experienced improvements in dyspnea scores (P lt; .010). Differences in mean scores over time significantly favored afatinib over chemotherapy for cough (P lt; .001) and dyspnea (P = .001). Afatinib showed significantly better mean scores over time in global health status/QoL (P = .015) and physical (P = .001), role (P = .004), and cognitive (P lt; .007) functioning compared with chemotherapy. Fatigue and nausea were worse with chemotherapy, whereas diarrhea, dysphagia, and sore mouth were worse with afatinib (all P = .01). Conclusion In patients with lung adenocarcinoma with EGFR mutations, first-line afatinib was associated with better control of cough and dyspnea compared with chemotherapy, although diarrhea, dysphagia, and sore mouth were worse. Global health status/QoL was also improved over time with afatinib compared with chemotherapy.

Development of Contact Lenses from a Biomaterial Point of View – Materials, Manufacture, and Clinical Application

Rigid lenses, which were originally made from glass (between 1888 and 1940) and later from polymethyl methacrylate or silicone acrylate materials, are uncomfortable to wear and are now seldom fitted to new patients. Contact lenses became a popular mode of ophthalmic refractive error correction following the discovery of the first hydrogel material – hydroxyethyl methacrylate – by Czech chemist Otto Wichterle in 1960. To satisfy the requirements for ocular biocompatibility, contact lenses must be transparent and optically stable (for clear vision), have a low elastic modulus (for good comfort), have a hydrophilic surface (for good wettability), and be permeable to certain metabolites, especially oxygen, to allow for normal corneal metabolism and respiration during lens wear. A major breakthrough in respect of the last of these requirements was the development of silicone hydrogel soft lenses in 1999 and techniques for making the surface hydrophilic. The vast majority of contact lenses distributed worldwide are mass-produced using cast molding, although spin casting is also used. These advanced mass-production techniques have facilitated the frequent disposal of contact lenses, leading to improvements in ocular health and fewer complications. More than one-third of all soft contact lenses sold today are designed to be discarded daily (i.e., ‘daily disposable’ lenses).

Simulating cooperative systems applications : a new complete architecture

For a decade, embedded driving assistance systems were mainly dedicated to the management of short time events (lane departure, collision avoidance, collision mitigation). Recently a great number of projects have been focused on cooperative embedded devices in order to extend environment perception. Handling an extended perception range is important in order to provide enough information for both path planning and co-pilot algorithms which need to anticipate events. To carry out such applications, simulation has been widely used. Simulation is efficient to estimate the benefits of Cooperative Systems (CS) based on Inter-Vehicular Communications (IVC). This paper presents a new and modular architecture built with the SiVIC simulator and the RTMaps™ multi-sensors prototyping platform. A set of improvements, implemented in SiVIC, are introduced in order to take into account IVC modelling and vehicles’ control. These 2 aspects have been tuned with on-road measurements to improve the realism of the scenarios. The results obtained from a freeway emergency braking scenario are discussed.

High-load transit line passenger transmission and productiveness efficiencies

Performance of urban transit systems may be quantified and assessed using transit capacity and productive capacity in planning, design and operational management activities. Bunker (4) defines important productive performance measures of an individual transit service and transit line, which are extended in this paper to quantify efficiency and operating fashion of transit services and lines. Comparison of a hypothetical bus line’s operation during a morning peak hour and daytime hour demonstrates the usefulness of productiveness efficiency and passenger transmission efficiency, passenger churn and average proportion line length traveled to the operator in understanding their services’ and lines’ productive performance, operating characteristics, and quality of service. Productiveness efficiency can flag potential pass-up activity under high load conditions, as well as ineffective resource deployment. Proportion line length traveled can directly measure operating fashion. These measures can be used to compare between lines/routes and, within a given line, various operating scenarios and time horizons to target improvements. The next research stage is investigating within-line variation using smart card passenger data and field observation of pass-ups. Insights will be used to further develop practical guidance to operators.

Whole-body cryotherapy : empirical evidence and theoretical perspectives

Whole-body cryotherapy (WBC) involves short exposures to air temperatures below –100°C. WBC is increasingly accessible to athletes, and is purported to enhance recovery after exercise and facilitate rehabilitation postinjury. Our objective was to review the efficacy and effectiveness of WBC using empirical evidence from controlled trials. We found ten relevant reports; the majority were based on small numbers of active athletes aged less than 35 years. Although WBC produces a large temperature gradient for tissue cooling, the relatively poor thermal conductivity of air prevents significant subcutaneous and core body cooling. There is weak evidence from controlled studies that WBC enhances antioxidant capacity and parasympathetic reactivation, and alters inflammatory pathways relevant to sports recovery. A series of small randomized studies found WBC offers improvements in subjective recovery and muscle soreness following metabolic or mechanical overload, but little benefit towards functional recovery. There is evidence from one study only that WBC may assist rehabilitation for adhesive capsulitis of the shoulder. There were no adverse events associated with WBC; however, studies did not seem to undertake active surveillance of predefined adverse events. Until further research is available, athletes should remain cognizant that less expensive modes of cryotherapy, such as local ice-pack application or cold-water immersion, offer comparable physiological and clinical effects to WBC.

The “virtual” producer in the recording studio : media networks in long distance peripheral performances

The producer has for many years been a central agent in recording studio sessions; the validation of this role was, in many ways, related to the producer’s physical presence in the studio, to a greater or lesser extent. However, improvements in the speed of digital networks have allowed studio sessions to be produced long-distance, in real-time, through communication programs such as Skype or REDIS. How does this impact on the role of the producer, a “nexus between the creative inspiration of the artist, the technology of the recording studio, and the commercial aspirations of the record company” (Howlett 2012)? From observations of a studio recording session in Lisbon produced through Skype from New York, this article focuses on the role of the producer in these relatively new recording contexts involving long distance media networks. Methodology involved participant observation carried out in Estúdios Namouche in Lisbon (where the session took place), as part of doctoral research. This ethnographic approach also included a number of semi-directed ethnographic interviews of the different actors in this scenario—musicians, recording engineers, composers and producers. As a theoretical framework, the research of De Zutter and Sawyer on Distributed Creativity is used, as the recording studio sets an example of “a cognitive system where […] tasks are not accomplished by separate individuals, but rather through the interactions of those individuals” (DeZutter 2009:4). Therefore, creativity often emerges as a result of this interaction.

Crucial roles for olfactory ensheathing cells and olfactory mucosal cells in the repair of damaged neural tracts

Olfactory ensheathing cells, the glial cells of the olfactory nervous system, exhibit unique growth-promoting and migratory properties that make them interesting candidates for cell therapies targeting neuronal injuries such as spinal cord injury. Transplantation of olfactory cells is feasible and safe in humans; however, functional outcomes are highly variable with some studies showing dramatic improvements and some no improvements at all. We propose that the reason for this is that the identity and purity of the cells is different in each individual study. We have shown that olfactory ensheathing cells are not a uniform cell population and that individual subpopulations of OECs are present in different regions of the olfactory nervous system, with strikingly different behaviors. Furthermore, the presence of fibroblasts and other cell types in the transplant can dramatically alter the behavior of the transplanted glial cells. Thus, a thorough characterization of the differences between olfactory ensheathing cell subpopulations and how the behavior of these cells is affected by the presence of other cell types is highly warranted.

A new approach for evaluating the benefits of smart grid development

In this paper, the inherent mechanism of benefits associated with smart grid development is examined based on the Pressure-State-Response (PSR) model from resource economics. The emerging types of technology brought up by smart grid development are taken as pressures. The improvements of the performance and efficiency of power system operation are taken as states. The effects of smart grid development on society are taken as responses. Then, a novel method for evaluating social benefits in energy saving and CO2 emission reduction from smart grid development is presented. Finally, the benefits in a province in northwest China is carried out by employing the developed evaluation system, and reasonable evaluation results are attained.

Optimization of an integrated model for automatic reduction and expansion of long queries

A long query provides more useful hints for searching relevant documents, but it is likely to introduce noise which affects retrieval performance. In order to smooth such adverse effect, it is important to reduce noisy terms, introduce and boost additional relevant terms. This paper presents a comprehensive framework, called Aspect Hidden Markov Model (AHMM), which integrates query reduction and expansion, for retrieval with long queries. It optimizes the probability distribution of query terms by utilizing intra-query term dependencies as well as the relationships between query terms and words observed in relevance feedback documents. Empirical evaluation on three large-scale TREC collections demonstrates that our approach, which is automatic, achieves salient improvements over various strong baselines, and also reaches a comparable performance to a state of the art method based on user’s interactive query term reduction and expansion.

GPU accelerated MCMC for modelling terrorist activity

The use of graphical processing unit (GPU) parallel processing is becoming a part of mainstream statistical practice. The reliance of Bayesian statistics on Markov Chain Monte Carlo (MCMC) methods makes the applicability of parallel processing not immediately obvious. It is illustrated that there are substantial gains in improved computational time for MCMC and other methods of evaluation by computing the likelihood using GPU parallel processing. Examples use data from the Global Terrorism Database to model terrorist activity in Colombia from 2000 through 2010 and a likelihood based on the explicit convolution of two negative-binomial processes. Results show decreases in computational time by a factor of over 200. Factors influencing these improvements and guidelines for programming parallel implementations of the likelihood are discussed.

Mapping Australian journalism culture : results from a survey of journalists’ role perceptions

Research on journalists’ characteristics, values, attitudes and role perceptions has expanded manifold since the first large-scale survey in the United States in the 1970s. Scholars around the world have investigated the work practices of a large variety of journalists, to the extent that we now have a sizeable body of evidence in this regard. Comparative research across cultures, however, has only recently begun to gain ground, with scholars interested in concepts of journalism culture in an age of globalisation. As part of a wider, cross-cultural effort, this study reports the results of a survey of 100 Australian journalists in order to paint a picture of the way journalists see their role in society. Such a study is important due to the relative absence of large-scale surveys of Australian journalists since Henningham’s (1993) seminal work. This paper reports some important trends in the Australian news media since the early 1990s, with improvements in gender balance and journalists now being older, better educated, and holding more leftist political views. In locating Australian journalism culture within the study’s framework, some long-held assumptions are reinforced, with journalists following traditional values of objectivity, passive reporting and the ideal of the fourth estate.