Validation of a contemporary prostate cancer grading system using prostate cancer death as outcome

BACKGROUND: Gleason scoring (GS) has major deficiencies and a novel system of five grade groups (GS⩽6; 3+4; 4+3; 8; ⩾9) has been recently agreed and included in the WHO 2016 classification. Although verified in radical prostatectomies using PSA relapse for outcome, it has not been validated using prostate cancer death as an outcome in biopsy series. There is debate whether an ‘overall' or ‘worst' GS in biopsies series should be used. METHODS: Nine hundred and eighty-eight prostate cancer biopsy cases were identified between 1990 and 2003, and treated conservatively. Diagnosis and grade was assigned to each core as well as an overall grade. Follow-up for prostate cancer death was until 31 December 2012. A log-rank test assessed univariable differences between the five grade groups based on overall and worst grade seen, and using univariable and multivariable Cox proportional hazards. Regression was used to quantify differences in outcome. RESULTS: Using both ‘worst' and ‘overall' GS yielded highly significant results on univariate and multivariate analysis with overall GS slightly but insignificantly outperforming worst GS. There was a strong correlation with the five grade groups and prostate cancer death. CONCLUSIONS: This is the largest conservatively treated prostate cancer cohort with long-term follow-up and contemporary assessment of grade. It validates the formation of five grade groups and suggests that the ‘worst' grade is a valid prognostic measure

A population-based cohort study on sun habits and endometrial cancer

Background:No large cohort study has examined the risk of endometrial cancer in relation to sun exposure.Methods:A population-based cohort study of 29 508 women who answered a questionnaire in 1990-92, of whom 24 098 responded to a follow-up enquiry in 2000-02. They were followed for an average of 15.5 years.Results:Among the 17 822 postmenopausal women included, 166 cases of endometrial cancer were diagnosed. We used a multivariate Cox regression analysis adjusting for age and other selected demographic variables to determine the risk of endometrial cancer. Women using sun beds >3 times per year reduced their hazard risk (HR) by 40% (0.6, 95% confidence interval (CI) 0.4-0.9) or by 50% when adjusting for body mass index or physical activity (HR 0.5, 95% CI 0.3-0.9), and those women who were sunbathing during summer reduced their risk by 20% (HR 0.8 95% CI 0.5-1.5) compared with women who did not expose themselves to the sun or to artificial sun (i.e., sun beds).Conclusion:Exposure to artificial sun by the use of sun beds >3 times per year was associated with a 40% reduction in the risk of endometrial cancer, probably by improving the vitamin D levels during winter.British Journal of Cancer advance online publication, 23 June 2009; doi:10.1038/sj.bjc.6605149 www.bjcancer.com

Unemployment expectations in an agent-based model with education

Why are unemployment expectations of the “man in the street” markedly different from professional forecasts? We present an agent-based model to explain this deep disconnection using boundedly rational agents with different levels of education. A good fit of empirical data is obtained under the assumptions that there is staggered update of information, agents update episodically their estimate and there is a fraction of households who always and stubbornly forecast that the unemployment is going to raise. The model also sheds light on the role of education and suggests that more educated agents update their information more often and less obstinately fixate on the worst possible forecast

Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass

Non invasive ventilation after extubation in paediatric patients: a preliminary study

<p>Abstract</p> <p>Background</p> <p>Non-invasive ventilation (NIV) may be useful after extubation in children. Our objective was to determine postextubation NIV characteristics and to identify risk factors of postextubation NIV failure.</p> <p>Methods</p> <p>A prospective observational study was conducted in an 8-bed pediatric intensive care unit (PICU). Following PICU protocol, NIV was applied to patients who had been mechanically ventilated for over 12 hours considered at high-risk of extubation failure -elective NIV (eNIV), immediately after extubation- or those who developed respiratory failure within 48 hours after extubation -rescue NIV (rNIV)-. Patients were categorized in subgroups according to their main underlying conditions. NIV was deemed successful when reintubation was avoided. Logistic regression analysis was performed in order to identify predictors of NIV failure.</p> <p>Results</p> <p>There were 41 episodes (rNIV in 20 episodes). Success rate was 50% in rNIV and 81% in eNIV (p = 0.037). We found significant differences in univariate analysis between success and failure groups in respiratory rate (RR) decrease at 6 hours, FiO₂at 1 hour and PO₂/FiO₂ratio at 6 hours. Neurologic condition was found to be associated with NIV failure. Multiple logistic regression analysis identified no variable as independent NIV outcome predictor.</p> <p>Conclusions</p> <p>Our data suggest that postextubation NIV seems to be useful in avoiding reintubation in high-risk children when applied immediately after extubation. NIV was more likely to fail when ARF has already developed (rNIV), when RR at 6 hours did not decrease and if oxygen requirements increased. Neurologic patients seem to be at higher risk of reintubation despite NIV use.</p

Measurement of GEp/GMp in ep -> ep to Q2 = 5.6 GeV2

The ratio of the electric and magnetic form factors of the proton, GEp/GMp, was measured at the Thomas Jefferson National Accelerator Facility (JLab) using the recoil polarization technique. The ratio of the form factors is directly proportional to the ratio of the transverse to longitudinal components of the polarization of the recoil proton in the elastic $\vec ep \to e\vec p$ reaction. The new data presented in this article span the range 3.5 < Q2 < 5.6 GeV2 and are well described by a linear Q2 fit. Also, the ratio QF2p/F1p reaches a constant value above Q2=2 GeV2.Comment: 6 pages, 4 figures Added two names to the main author lis

Diagnostic aids in the screening of oral cancer

The World Health Organization has clearly indentified prevention and early detection as major objectives in the control of the oral cancer burden worldwide. At the present time, screening of oral cancer and its pre-invasive intra-epithelial stages, as well as its early detection, is still largely based on visual examination of the mouth. There is strong available evidence to suggest that visual inspection of the oral mucosa is effective in reducing mortality from oral cancer in individuals exposed to risk factors. Simple visual examination, however, is well known to be limited by subjective interpretation and by the potential, albeit rare, occurrence of dysplasia and early OSCC within areas of normal-looking oral mucosa. As a consequence, adjunctive techniques have been suggested to increase our ability to differentiate between benign abnormalities and dysplastic/malignant changes as well as to identify areas of dysplasia/early OSCC that are not visible to naked eye. These include the use of toluidine blue, brush biopsy, chemiluminescence and tissue autofluorescence. The present paper reviews the evidence supporting the efficacy of the aforementioned techniques in improving the identification of dysplastic/malignant changes of the oral mucosa. We conclude that available studies have shown promising results, but strong evidence to support the use of oral cancer diagnostic aids is still lacking. Further research with clear objectives, well-defined population cohorts, and sound methodology is strongly required

Listening In on the Past: What Can Otolith δ18O Values Really Tell Us about the Environmental History of Fishes?

Oxygen isotope ratios from fish otoliths are used to discriminate marine stocks and reconstruct past climate, assuming that variations in otolith δ18O values closely reflect differences in temperature history of fish when accounting for salinity induced variability in water δ18O. To investigate this, we exploited the environmental and migratory data gathered from a decade using archival tags to study the behaviour of adult plaice (Pleuronectes platessa L.) in the North Sea. Based on the tag-derived monthly distributions of the fish and corresponding temperature and salinity estimates modelled across three consecutive years, we first predicted annual otolith δ18O values for three geographically discrete offshore sub-stocks, using three alternative plausible scenarios for otolith growth. Comparison of predicted vs. measured annual δ18O values demonstrated >96% correct prediction of sub-stock membership, irrespective of the otolith growth scenario. Pronounced inter-stock differences in δ18O values, notably in summer, provide a robust marker for reconstructing broad-scale plaice distribution in the North Sea. However, although largely congruent, measured and predicted annual δ18O values of did not fully match. Small, but consistent, offsets were also observed between individual high-resolution otolith δ18O values measured during tag recording time and corresponding δ18O predictions using concomitant tag-recorded temperatures and location-specific salinity estimates. The nature of the shifts differed among sub-stocks, suggesting specific vital effects linked to variation in physiological response to temperature. Therefore, although otolith δ18O in free-ranging fish largely reflects environmental temperature and salinity, we counsel prudence when interpreting otolith δ18O data for stock discrimination or temperature reconstruction until the mechanisms underpinning otolith δ18O signature acquisition, and associated variation, are clarified

A Diamond Nanowire Single Photon Antenna

The development of a robust light source that emits one photon at a time is an outstanding challenge in quantum science and technology. Here, at the transition from many to single photon optical communication systems, fully quantum mechanical effects may be utilized to achieve new capabilities, most notably perfectly secure communication via quantum cryptography. Practical implementations place stringent requirements on the device properties, including stable photon generation, room temperature operation, and efficient extraction of many photons. Single photon light emitting devices based on fluorescent dye molecules, quantum dots, and carbon nanotube material systems have all been explored, but none have simultaneously demonstrated all criteria. Here, we describe the design, fabrication, and characterization of a bright source of single photons consisting of an individual Nitrogen-vacancy color center (NV center) in a diamond nanowire operating in ambient conditions. The nanowire plays a positive role in increasing the number of single photons collected from the NV center by an order of magnitude over devices based on bulk diamond crystals, and allows operation at an order of magnitude lower power levels. This result enables a new class of nanostructured diamond devices for room temperature photonic and quantum information processing applications, and will also impact fields as diverse as biological and chemical sensing, opto-mechanics, and scanning-probe microscopy.Comment: 16 pages, 4 figures, v2: Includes improved reference list; modified figure 1 to show a large array of NW and FDTD simulation of field profile; direct experimental comparsion of several bulk/NW devices in figure