From laboratory tests to field trials: a review of cathodic protection and microbially influenced corrosion.

Cathodic protection (CP), an electrochemical method for managing corrosion, is widely used in many industries in both marine and buried environments. However, literature surrounding cathodic protection and its ability to prevent microbially influenced corrosion (MIC) is mixed. This review describes the mechanics of CP, how CP may influence MIC, and collates and summarises tests on CP and MIC reported in literature. The aim of the review is to identify any trends and knowledge gaps requiring further study. While the outcomes of CP testing are generally mixed, some trends can be seen and, overall, MIC is detrimental to the protective effects of CP, with CP being less effective when used according to current international standards. Tests conducted in the field or with mix communities of microbes showed that CP could be effective at preventing MIC, while tests with sulfate-reducing bacteria generally proved CP to be highly ineffective. It was commonly seen that the effectiveness of CP can be improved by increasing polarization, to potentials as low as -1000 mV (Ag/AgCl). However, a balance does need to be met via careful monitoring to ensure negative side effects of over protection do not become a major problem.

Photonic metacrystal: design methodology and experimental characterization.

We report a design methodology for creating high-performance photonic crystals with arbitrary geometric shapes. This design approach enables the inclusion of subwavelength shapes into the photonic crystal unit cell, synergistically combining metamaterials concepts with on-chip guided-wave photonics. Accordingly, we use the term "photonic metacrystal" to describe this class of photonic structures. Photonic metacrystals exploiting three different design freedoms are demonstrated experimentally. With these additional degrees of freedom in the design space, photonic metacrystals enable added control of light-matter interactions and hold the promise of significantly increasing temporal confinement in all-dielectric metamaterials.

Comparison of Grenz ray and photodynamic therapy for field treatment of actinic keratoses on the forearm: A case series.

BACKGROUND: Actinic Keratosis is an intraepidermal neoplasm that represents the second most common reason for dermatologic visits in the United States. Sustained clearance with existing therapies is highly variable. OBJECTIVE: To assess the effects of combination and monotherapy with photodynamic therapy (PDT), grenz ray therapy, and PDT with microneedling (microchannel skin system) for actinic damage of the dorsal forearms and hands. METHODS: Full ethics approval was obtained through a Human Subjects Committee. Four patients with diffuse actinic field damage on their forearms and hands were recruited for the study. The dorsal forearm and hand from the elbow to the metacarpophalangeal joint were divided into four equal sections. Section 1 was treated with PDT. Section 2 was treated with grenz ray. Section 3 was treated with PDT plus microneedling. Section 4 was treated with grenz ray and PDT with microneedling. Lesion counts were recorded with transparent grids, photographed and evaluated by the same investigator at baseline, 1, 2, 3 and 6 months. RESULTS: At month 6 post treatment, lesion counts, as a per cent reduction from baseline, were 91.7% in section 1 (PDT); 97.3% in section 2 (grenz ray); 92.9% in section 3 (PDT + microneedle); and 93.9% in section 4 (grenz ray + PDT + microneedle). CONCLUSION: The greatest reduction occurred in the grenz ray monotherapy section and the second greatest reduction in the grenz ray, PDT, microneedling section. Further research on the efficacy of grenz ray therapy for field treatment of actinic keratosis of the forearms and hands is needed.

Online symptom checker diagnostic and triage accuracy for HIV and hepatitis C.

We sought to address the prior limitations of symptom checker accuracy by analysing the diagnostic and triage feasibility of online symptom checkers using a consecutive series of real-life emergency department (ED) patient encounters, and addressing a complex patient population - those with hepatitis C or HIV. We aimed to study the diagnostic and triage accuracy of these symptom checkers in relation to an emergency room physician-determined diagnosis. An ED retrospective analysis was performed on 8363 consecutive adult patients. Eligible patients included: 90 HIV, 67 hepatitis C, 11 both HIV and hepatitis C. Five online symptom checkers were utilised for diagnosis (Mayo Clinic, WebMD, Symptomate, Symcat, Isabel), three with triage capabilities. Symptom checker output was compared with ED physician-determined diagnosis data in regards to diagnostic accuracy and differential diagnosis listing, along with triage advice. All symptom checkers, whether for combined HIV and hepatitis C, HIV alone or hepatitis C alone had poor diagnostic accuracy in regards to Top1 (<20%), Top3 (<35%), Top10 (<40%), Listed at All (<45%). Significant variations existed for each individual symptom checker, as some appeared more accurate for listing the diagnosis in the top of the differential, vs. others more apt to list the diagnosis at all. In regards to ED triage data, a significantly higher percentage of hepatitis C patients (59.7%; 40/67) were found to have an initial diagnosis with emergent criteria than HIV patients (35.6%; 32/90). Symptom checker diagnostic capabilities are quite inferior to physician diagnostic capabilities. Complex patients such as those with HIV or hepatitis C may carry a more specific differential diagnosis, warranting symptom checkers to have diagnostic algorithms accounting for such complexity. Symptom checkers carry the potential for real-time epidemiologic monitoring of patient symptoms, as symptom entries and subsequent symptom checker diagnosis could allow health officials a means to track illnesses in specific patient populations and geographic regions. In order to do this, accurate and reliable symptom checkers are warranted.

Cost-effectiveness of the SQ HDM SLIT-tablet for the treatment of allergic asthma in three Eastern European Countries.

Summary: Background.The SQ® house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet (ACARIZAX®, ALK-Abelló A/S, Hørsholm, Denmark) is an allergy immunotherapy tablet for people with allergic respiratory disease. This analysis aims to assess the cost-effectiveness of the SQ HDM SLIT-tablet from the perspective of three Eastern European countries: Czech Republic, Poland and Slovakia. Methods.A cost-utility model per country was developed, which compared the SQ HDM SLIT-tablet as add-on to pharmacotherapy with pharmacotherapy alone in patients with HDM allergic asthma (AA) over a five year time horizon. The effectiveness of the two interventions was based on the results from a large-scale randomised controlled trial. In the models, annual costs and quality-adjusted life year (QALY) scores from the trial were extrapolated over a five year period, and the incremental cost-effectiveness ratios (ICERs) were estimated. One-way deterministic sensitivity and scenario analyses were undertaken. Results.The SQ HDM SLIT-tablet is cost-effective in all three markets over the five year time horizon (ICERs of less than € 10,000 per additional QALY). Treatment with the SQ HDM SLIT-tablet improves patient outcomes, with QALY gains of 0.35, versus pharmacotherapy only. In all three countries, the SQ HDM SLIT-tablet also incurs increased costs compared to pharma-cotherapy treatment only. The sensitivity analysis identified utility values from the clinical trial as the main driver of the model results. Conclusion.The SQ HDM SLIT-tablet is a cost-effective treatment option for people with HDM AA in three different health care settings in Eastern Europe.

Modulator figure of merit for short reach data links.

The traditional Mach-Zehnder modulator (MZM) figure of merit (FOM) has been defined as (Vπ2)/υ3dBe, and works effectively for LiNbO3 long haul modulators. However, for plasma dispersion based electro-optic modulators, or any modulator that has an inherent relationship between its bandwidth, required drive voltage, and optical insertion loss/gain, this FOM is inappropriate. This is particularly true for short reach links with no optical amplification. In the following, we propose a new modulator FOM (M-FOM) based on device metrics that are essential for short-reach links, such as the peak-to-peak drive voltage, modulator rise-fall time, and relative optical modulation amplitude. Link sensitivity measurements from two MZMs that have different bandwidths and optical losses are compared using our M-FOM to demonstrate its utility. Furthermore, we present a novel application protocol of our M-FOM to provide deeper insight into the relative system impact that modulator performance has on data links with no optical amplification, by taking the ratio of M-FOMs from two modulators driven with the same radio frequency drive power.

Increased risk of influenza among vaccinated adults who are obese.

BACKGROUND: Influenza infects 5-15% of the global population each year, and obesity has been shown to be an independent risk factor for increased influenza-related complications including hospitalization and death. However, the risk of developing influenza or influenza-like illness (ILI) in a vaccinated obese adult population has not been addressed. OBJECTIVE: This study evaluated whether obesity was associated with increased risk of influenza and ILI among vaccinated adults. SUBJECTS AND METHODS: During the 2013-2014 and 2014-2015 influenza seasons, we recruited 1042 subjects to a prospective observational study of trivalent inactivated influenza vaccine (IIV3) in adults. A total of 1022 subjects completed the study. Assessments of relative risk for laboratory confirmed influenza and ILI were determined based on body mass index. Seroconversion and seroprotection rates were determined using prevaccination and 26-35 days post vaccination serum samples. Recruitment criteria for this study were adults 18 years of age and older receiving the seasonal trivalent inactivated influenza vaccine (IIV3) for the years 2013-2014 and 2014-2015. Exclusion criteria were immunosuppressive diseases, use of immunomodulatory or immunosuppressive drugs, acute febrile illness, history of Guillain-Barre syndrome, use of theophylline preparations or use of warfarin. RESULTS: Among obese, 9.8% had either confirmed influenza or influenza-like-illness compared with 5.1% of healthy weight participants. Compared with vaccinated healthy weight, obese participants had double the risk of developing influenza or ILI (relative risk=2.01, 95% CI 1.12, 3.60, P=0.020). Seroconversion or seroprotection rates were not different between healthy weight and obese adults with influenza or ILI. CONCLUSIONS: Despite robust serological responses, vaccinated obese adults are twice as likely to develop influenza and ILI compared with healthy weight adults. This finding challenges the current standard for correlates of protection, suggesting use of antibody titers to determine vaccine effectiveness in an obese population may provide misleading information.

Revisiting Milan cervical cancer study: Do the original findings hold in the era of chemotherapy?

BACKGROUND: The primary treatment of early stage cervical carcinoma (IB-IIA) is either surgery or radiation therapy based on the pivotal Milan randomized study published twenty years ago. In the presence of high-risk features, the gold standard treatment is concurrent chemotherapy and radiation therapy (CRT) whether it is the in the postoperative or the definitive setting. Using the National Cancer Data Base (NCDB), the goal of our study is to compare the outcomes of surgery and radiation therapy in the chemotherapy era. METHODS: Between 2004 and 2013, 5478 patients diagnosed with early stage cervical cancer were divided into 2 groups based on their primary treatment: non-surgical (n=1980) and surgical groups (n=3498). The distribution of patient/tumor characteristics and treatment variables with their relation to overall survival and proportional regression models were assessed to investigate the superiority of one approach over the other. Propensity score analysis adjusted for imbalance of covariates to create a well-matched-patient cohort. FINDINGS: At 46months median follow-up, the 5-year overall survival was similar between both groups (73·8% vs. 75.7%; p=0.619) after applying propensity score analysis. On multivariate analysis, high Charlson comorbidity score, stage IIA disease, larger tumor size, positive lymph nodes and high-grade disease were significant predictors of poor outcome while older age and treatment approach were not. INTERPRETATION: Our analysis suggests that surgery (followed by adjuvant RT or CRT) and definitive radiotherapy (with or without chemotherapy) result in equivalent survival. Prospective studies are warranted to establish this paradigm in the chemotherapy era.

Cost utility analysis of the SQ(®) HDM SLIT-tablet in house dust mite allergic asthma patients in a German setting.

BACKGROUND: Asthma affects an estimated 300 million people worldwide with the condition associated with significant healthcare utilisation costs and a large impact on patient quality of life. The SQ(®) HDM SLIT-tablet (ACARIZAX(®), Hørsholm, Denmark) is a sublingually administered allergy immunotherapy tablet for house dust mite allergic asthma and allergic rhinitis and has recently been licensed in Europe. OBJECTIVE: To assess the cost-effectiveness of ACARIZAX plus pharmacotherapy versus placebo plus pharmacotherapy in patients with house dust mite allergic asthma that is uncontrolled by inhaled corticosteroids, in a German setting. Eligible patients should also have symptoms of mild to severe allergic rhinitis. METHODS: A cost utility analysis was undertaken, based on the results of a European phase III randomised controlled trial, in which ACARIZAX was compared with placebo with both treatment groups also receiving pharmacotherapy in the form of inhaled corticosteroids and short-acting ß2-agonists. Cost and quality-adjusted life years from the trial were extrapolated over a nine year time horizon and the incremental cost-effectiveness ratio calculated to compare treatment options. RESULTS: ACARIZAX plus pharmacotherapy was estimated to generate 6.16 quality-adjusted life years per patient at a cost of €5658, compared with 5.50 quality-adjusted life years (QALYs) at a cost of €2985 for placebo plus pharmacotherapy. This equated to an incremental cost of €2673, incremental QALYs of 0.66 and an incremental cost-effectiveness ratio (ICER) of €4041. The ICER was, therefore, substantially lower than the €40,000 willingness-to-pay threshold per QALY adopted for the analysis. Deterministic sensitivity analyses indicate the results are most sensitive to the utility score of ACARIZAX patients during years 2 and 3 of treatment. CONCLUSION: This analysis indicates that ACARIZAX plus pharmacotherapy is cost-effective compared with placebo plus pharmacotherapy for house dust mite allergic asthma patients in Germany. If a disease-modifying effect can be proven the results of this analysis may underestimate the true benefits of ACARIZAX.

Cytoplasmic PML promotes TGF-ß-associated epithelial-mesenchymal transition and invasion in prostate cancer.

Epithelial-mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-ß signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-ß signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-ß canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-ß signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit.

Phytoplankton biomass and composition in a well-flushed, sub-tropical estuary: The contrasting effects of hydrology, nutrient loads and allochthonous influences.

The primary objective of this study was to examine trends in phytoplankton biomass and species composition under varying nutrient load and hydrologic regimes in the Guana Tolomato Matanzas estuary (GTM), a well-flushed sub-tropical estuary located on the northeast coast of Florida. The GTM contains both regions of significant human influence and pristine areas with only modest development, providing a test case for comparing and contrasting phytoplankton community dynamics under varying degrees of nutrient load. Water temperature, salinity, Secchi disk depth, nutrient concentrations and chlorophyll concentrations were determined on a monthly basis from 2002 to 2012 at three representative sampling sites in the GTM. In addition, microscopic analyses of phytoplankton assemblages were carried out monthly for a five year period from 2005 through 2009 at all three sites. Results of this study indicate that phytoplankton biomass and composition in the GTM are strongly influenced by hydrologic factors, such as water residence times and tidal exchanges of coastal waters, which in turn are affected by shifts in climatic conditions, most prominently rainfall levels. These influences are exemplified by the observation that the region of the GTM with the longest water residence times but lowest nutrient loads exhibited the highest phytoplankton peaks of autochthonous origin. The incursion of a coastal bloom of the toxic dinoflagellate Karenia brevis into the GTM in 2007 demonstrates the potential importance of allochthonous influences on the ecosystem.

Distributed electrode Mach-Zehnder modulator with double-pass phase shifters and integrated inductors.

A novel high-speed Mach-Zehnder modulator (MZM) fully integrated into a 90 nm CMOS process is presented. The MZM features 'double-pass' optical phase shifter segments, and the first use of integrated inductors in a 'velocity-matched' distributed-electrode configuration.

Microbiota and host determinants of behavioural phenotype in maternally separated mice.

Early-life stress is a determinant of vulnerability to a variety of disorders that include dysfunction of the brain and gut. Here we exploit a model of early-life stress, maternal separation (MS) in mice, to investigate the role of the intestinal microbiota in the development of impaired gut function and altered behaviour later in life. Using germ-free and specific pathogen-free mice, we demonstrate that MS alters the hypothalamic-pituitary-adrenal axis and colonic cholinergic neural regulation in a microbiota-independent fashion. However, microbiota is required for the induction of anxiety-like behaviour and behavioural despair. Colonization of adult germ-free MS and control mice with the same microbiota produces distinct microbial profiles, which are associated with altered behaviour in MS, but not in control mice. These results indicate that MS-induced changes in host physiology lead to intestinal dysbiosis, which is a critical determinant of the abnormal behaviour that characterizes this model of early-life stress.

Generation of 3.6 µm radiation and telecom-band amplification by four-wave mixing in a silicon waveguide with normal group velocity dispersion.

Mid-infrared light generation through four-wave mixing-based frequency down-conversion in a normal group velocity dispersion silicon waveguide is demonstrated. A telecom-wavelength signal is down-converted across more than 1.2 octaves using a pump at 2190 nm in a 1 cm-long waveguide. At the same time, a 13 dB on-chip parametric gain of the telecom signal is obtained.

Coupling modulation of microrings at rates beyond the linewidth limit.

We demonstrate optical modulation rates exceeding the conventional cavity linewidth limit using a silicon coupling modulated microring. Small-signal measurements show coupling modulation was free of the parasitic cavity linewidth limitations at rates at least 6× the cavity linewidth. Eye diagram measurements show coupling modulation achieved data rates > 2× the rate attainable by conventional intracavity phase modulation. We propose to use DC-balanced encoding to mitigate the inter-symbol interference in coupling modulation. Analysis shows that coupling modulation can be more efficient than intracavity modulation for large output swings and high-Q resonators. Coupling modulation enables very high-Q resonant modulators to be simultaneously low-power and high-speed, features which are mutually incompatible in typical resonant modulators studied to date.

A possible chemopreventive role for photodynamic therapy in Gorlin syndrome: a report of basal cell carcinoma reduction and review of literature.

Multiple basal cell carcinomas (BCC) are a significant cause of morbidity and disfigurement in patients with naevoid basal cell carcinoma syndrome (NBCCS). Chemopreventive strategies are needed to reduce the formation of new BCC in these patients. Appropriate evidence-based guidelines for photodynamic therapy chemoprevention in NBCCS do not exist. We herein report one patient treated with methyl aminolevulinate PDT with red light (630 nm) activation to continue sustained chemoprevention following other BCC chemopreventive modalities and a relevant literature review.