An Update on Grading of Salivary Gland Carcinomas

Histologic grade is a significant predictor of outcome in salivary gland carcinomas. However, the sheer variety of tumor type and the rarity of these tumors pose challenges to devising highly predictive grading schemes. As our knowledge base has evolved, it is clear that carcinoma ex pleomorphic adenoma is not automatically a high grade tumor as is traditionally suggested. These tumors should be further qualified as to type/grade of carcinoma and extent, since intracapsular and minimally invasive carcinomas ex pleomorphic adenoma behave favorably. The two carcinoma types for which grading schemes are common include adenoid cystic carcinoma and mucoepidermoid carcinoma. Adenoid cystic carcinomas are graded based solely on pattern with solid components portending a worse prognosis. Occasionally, adenoid cystic carcinomas may undergo transformation to pleomorphic high grade carcinomas. This feature confers a high propensity for lymph node metastasis and should thus be reported to alert the clinical team. Mucoepidermoid carcinomas are graded in a three tier fashion based on a constellation of features including cystic component, border, mitoses, anaplasia, and perineural invasion among others. All grading schemes are somewhat cumbersome, intimidating and occasionally ambiguous, but evidence suggests that using a scheme consistently shows greater reproducibility than using an intuitive approach. The intermediate grade category demonstrates the most variability between grading systems and thus the most controversy in management. In the AFIP system intermediate grade tumors cluster with high grade tumors, while in the Brandwein system, they cluster with low grade tumors

The edges of understanding

A culture's icons are a window onto its soul. Few would disagree that, in the culture of molecular biology that dominated much of the life sciences for the last third of the 20th century, the dominant icon was the double helix. In the present, post-modern, 'systems biology' era, however, it is, arguably, the hairball

Clinical significance of VEGF-A, -C and -D expression in esophageal malignancies

Vascular endothelial growth factors ( VEGF)- A, - C and - D are members of the proangiogenic VEGF family of glycoproteins. VEGF-A is known to be the most important angiogenic factor under physiological and pathological conditions, while VEGF-C and VEGF-D are implicated in the development and sprouting of lymphatic vessels, so called lymphangiogenesis. Local tumor progression, lymph node metastases and hematogenous tumor spread are important prognostic factors for esophageal carcinoma ( EC), one of the most lethal malignancies throughout the world. We found solid evidence in the literature that VEGF expression contributes to tumor angiogenesis, tumor progression and lymph node metastasis in esophageal squamous cell carcinoma ( SCC), and many authors could show a prognostic value for VEGF-assessment. In adenocarcinoma (AC) of the esophagus angiogenic properties are acquired in early stages, particularly in precancerous lesions like Barrett's dysplasia. However, VEGF expression fails to give prognostic information in AC of the esophagus. VEGF-C and VEGF-D were detected in SCC and dysplastic lesions, but not in normal mucosa of the esophagus. VEGF-C expression might be associated with lymphatic tumor invasion, lymph node metastases and advanced disease in esophageal SCC and AC. Therapeutic interference with VEGF signaling may prove to be a promising way of anti-angiogenic co-treatment in esophageal carcinoma. However, concrete clinical data are still pending

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Influence of Different Application of Lubricants on Wear and Pre-existing Rolling Contact Fatigue Cracks of Rail Materials

Rolling contact fatigue (RCF) of rail can be a significant problem affecting safety and maintenance. Rail materials have been optimized to reduce it, but not enough is known about how friction management products applied to the rail affect crack growth. This study presents experimental results carried out to explore the influence of different lubricants and application orders on wear and pre-existing RCF cracks in rail materials. The results indicate that the types or properties of lubricants have a vital role in the wear rate and fatigue crack growth characteristics of rail materials after conditioning with 5000 dry cycles to initiate cracks. Using a different application order of two lubricants has a significant influence on the crack growth angles in the rail rollers

Hospital service areas – a new tool for health care planning in Switzerland

BACKGROUND: The description of patient travel patterns and variations in health care utilization may guide a sound health care planning process. In order to accurately describe these differences across regions with homogeneous populations, small area analysis (SAA) has proved as a valuable tool to create appropriate area models. This paper presents the methodology to create and characterize population-based hospital service areas (HSAs) for Switzerland. METHODS: We employed federal hospital discharge data to perform a patient origin study using small area analysis. Each of 605 residential regions was assigned to one of 215 hospital provider regions where the most frequent number of discharges took place. HSAs were characterized geographically, demographically, and through health utilization indices and rates that describe hospital use. We introduced novel planning variables extracted from the patient origin study and investigated relationships among health utilization indices and rates to understand patient travel patterns for hospital use. Results were visualized as maps in a geographic information system (GIS). RESULTS: We obtained 100 HSAs using a patient origin matrix containing over four million discharges. HSAs had diverse demographic and geographic characteristics. Urban HSAs had above average population sizes, while mountainous HSAs were scarcely populated but larger in size. We found higher localization of care in urban HSAs and in mountainous HSAs. Half of the Swiss population lives in service areas where 65% of hospital care is provided by local hospitals. CONCLUSION: Health utilization indices and rates demonstrated patient travel patterns that merit more detailed analyses in light of political, infrastructural and developmental determinants. HSAs and health utilization indices provide valuable information for health care planning. They will be used to study variation phenomena in Swiss health care

Wanted dead or alive : high diversity of macroinvertebrates associated with living and ’dead’ Posidonia oceanica matte

The Mediterranean endemic seagrass Posidonia oceanica forms beds characterised by a dense leaf canopy and a thick root-rhizome ‘matte’. Death of P. oceanica shoots leads to exposure of the underlying matte, which can persist for many years, and is termed ‘dead’ matte. Traditionally, dead matte has been regarded as a degraded habitat. To test whether this assumption was true, the motile macroinvertebrates of adjacent living (with shoots) and dead (without shoots) matte of P. oceanica were sampled in four different plots located at the same depth (5–6 m) in Mellieha Bay, Malta (central Mediterranean). The total number of species and abundance were significantly higher (ANOVA; P<0.05 and P<0.01, respectively) in the dead matte than in living P. oceanica matte, despite the presence of the foliar canopy in the latter. Multivariate analysis (MDS) clearly showed two main groups of assemblages, corresponding to the two matte types. The amphipods Leptocheirus guttatus and Maera grossimana, and the polychaete Nereis rava contributed most to the dissimilarity between the two different matte types. Several unique properties of the dead matte contributing to the unexpected higher number of species and abundance of motile macroinvertebrates associated with this habitat are discussed. The findings have important implications for the conservation of bare P. oceanica matte, which has been generally viewed as a habitat of low ecological value.peer-reviewe

Impact of efalizumab on patient-reported outcomes in high-need psoriasis patients: results of the international, randomized, placebo-controlled Phase III Clinical Experience Acquired with Raptiva (CLEAR) trial [NCT00256139]

BACKGROUND: Chronic psoriasis can negatively affect patients' lives. Assessing the impact of treatment on different aspects of a patient's health-related quality of life (HRQOL) is therefore important and relevant in trials of anti-psoriasis agents. The recombinant humanized IgG(1 )monoclonal antibody efalizumab targets multiple T-cell-dependent steps in the immunopathogenesis of psoriasis. Efalizumab has demonstrated safety and efficacy in several clinical trials, and improves patients' quality of life. Objective: To evaluate the impact of efalizumab on HRQOL and other patient-reported outcomes in patients with moderate to severe plaque psoriasis, including a large cohort of High-Need patients for whom at least 2 other systemic therapies were unsuitable because of lack of efficacy, intolerance, or contraindication. METHODS: A total of 793 patients were randomized in a 2:1 ratio to receive efalizumab 1 mg/kg/wk (n = 529) or placebo (n = 264) for 12 weeks. The study population included 526 High-Need patients (342 efalizumab, 184 placebo). The treatment was evaluated by patients using the HRQOL assessment tools Short Form-36 (SF-36) and Dermatology Life Quality Index (DLQI). Other patient-reported assessments included the Psoriasis Symptom Assessment (PSA), a visual analog scale (VAS) for itching, and the Patient's Global Psoriasis Assessment (PGPA). RESULTS: Efalizumab was associated with improvements at Week 12 from baseline in patient-reported outcomes, both in the total study population and in the High-Need cohort. Among all efalizumab-treated patients, the DLQI improved by 5.7 points from baseline to Week 12, relative to an improvement of 2.3 points for placebo patients (P < .001). Corresponding improvements in DLQI in the High-Need cohort were 5.4 points for efalizumab compared to 2.3 for placebo (P < .001). Improvements from baseline on the SF-36, PSA, PGPA, and itching VAS at Week 12 were also significantly greater in efalizumab-treated patients than for placebo. CONCLUSION: A 12-week course of efalizumab improved HRQOL and other patient-reported outcomes in patients with moderate to severe plaque psoriasis. The benefits of efalizumab therapy in High-Need patients were similar to those observed in the total study population, indicating that the beneficial impact of efalizumab on QOL is consistent regardless of disease severity, prior therapy, or contraindications to previous therapies

The second data release of the INT Photometric Ha Survey of the Northern Galactic Plane (IPHAS DR2)

The INT/WFC Photometric Hα Survey of the Northern Galactic Plane (IPHAS) is a 1800 deg2 imaging survey covering Galactic latitudes |b| < 5° and longitudes ℓ = 30°–215° in the r, i, and Hα filters using the Wide Field Camera (WFC) on the 2.5-m Isaac Newton Telescope (INT) in La Palma. We present the first quality-controlled and globally calibrated source catalogue derived from the survey, providing single-epoch photometry for 219 million unique sources across 92 per cent of the footprint. The observations were carried out between 2003 and 2012 at a median seeing of 1.1 arcsec (sampled at 0.33 arcsec pixel−1) and to a mean 5σ depth of 21.2 (r), 20.0 (i), and 20.3 (Hα) in the Vega magnitude system. We explain the data reduction and quality control procedures, describe and test the global re-calibration, and detail the construction of the new catalogue. We show that the new calibration is accurate to 0.03 mag (root mean square) and recommend a series of quality criteria to select accurate data from the catalogue. Finally, we demonstrate the ability of the catalogue's unique (r − Hα, r − i) diagram to (i) characterize stellar populations and extinction regimes towards different Galactic sightlines and (ii) select and quantify Hα emission-line objects. IPHAS is the first survey to offer comprehensive CCD photometry of point sources across the Galactic plane at visible wavelengths, providing the much-needed counterpart to recent infrared surveys

Nicotine patch preloading for smoking cessation (the preloading trial): study protocol for a randomized controlled trial

Background: The use of nicotine replacement therapy before quitting smoking is called nicotine preloading. Standard smoking cessation protocols suggest commencing nicotine replacement therapy only on the first day of quitting smoking (quit day) aiming to reduce withdrawal symptoms and craving. However, other, more successful smoking cessation pharmacotherapies are used prior to the quit day as well as after. Nicotine preloading could improve quit rates by reducing satisfaction from smoking prior to quitting and breaking the association between smoking and reward. A systematic literature review suggests that evidence for the effectiveness of preloading is inconclusive and further trials are needed. Methods/Design: This is a study protocol for a multicenter, non-blinded, randomized controlled trial based in the United Kingdom, enrolling 1786 smokers who want to quit, funded by the National Institute for Health Research, Health Technology Assessment program, and sponsored by the University of Oxford. Participants will primarily be recruited through general practices and smoking cessation clinics, and randomized (1:1) either to use 21 mg nicotine patches, or not, for four weeks before quitting, whilst smoking as normal. All participants will be referred to receive standard smoking cessation service support. Follow-ups will take place at one week, four weeks, six months and 12 months after quit day. The primary outcome will be prolonged, biochemically verified six-month abstinence. Additional outcomes will include point prevalence abstinence and abstinence of four-week and 12-month duration, side effects, costs of treatment, and markers of potential mediators and moderators of the preloading effect. Discussion: This large trial will add substantially to evidence on the effectiveness of nicotine preloading, but also on its cost effectiveness and potential mediators, which have not been investigated in detail previously. A range of recruitment strategies have been considered to try and compensate for any challenges encountered in recruiting the large sample, and the multicentre design means that knowledge can be shared between recruitment teams. The pragmatic study design means that results will give a realistic estimate of the success of the intervention if it were to be rolled out as part of standard smoking cessation service practice. Trial registration: Current Controlled Trials ISRCTN33031001. Registered 27 April 2012