204 research outputs found

    Role of immunohistochemistry for interobserver agreement of Peritoneal Regression Grading Score in peritoneal metastasis.

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    Pressurized intraperitoneal aerosol chemotherapy (PIPAC)-directed therapy is a new treatment option for peritoneal metastasis (PM). The 4-tiered Peritoneal Regression Grading Score (PRGS) has been proposed for assessment of histological treatment response. We aimed to evaluate the effect of immunohistochemistry (IHC) on interobserver agreement of the PRGS. Hematoxylin and eosin (H&E)-stained and IHC-stained slides (n = 662) from 331 peritoneal quadrant biopsies (QBs) taken prior to 99 PIPAC procedures performed on 33 patients were digitalized and uploaded to a web library. Eight raters (five consultants and three residents) assessed the PRGS, and Krippendorff's alpha coefficients (Îą) were calculated. Results (IHC-PRGS) were compared with data published in 2019, using H&E-stained slides only (H&E-PRGS). Overall, agreement for IHC-PRGS was substantial to almost perfect. Agreement (all raters) regarding single QBs after treatment was substantial for IHC-PRGS (Îą = 0.69, 95% confidence interval [CI] = 0.66-0.72) and moderate for H&E-PRGS (Îą = 0.60, 95% CI = 0.56-0.64). Agreement (all raters) regarding the mean PRGS per QB set after treatment was higher for IHC-PRGS (Îą = 0.78, 95% CI = 0.73-0.83) than for H&E-PRGS (Îą = 0.71, 95% CI = 0.64-0.78). Among residents, agreement was almost perfect for IHC-PRGS and substantial for H&E-PRGS. Agreement (all raters) regarding maximum PRGS per QB set after treatment was substantial for IHC-PRGS (Îą = 0.61, 95% CI = 0.54-0.68) and moderate for H&E-PRGS (Îą = 0.60, 95% CI = 0.53-0.66). Among residents, agreement was substantial for IHC-PRGS (Îą = 0.66, 95% CI = 0.57-0.75) and moderate for H&E-PRGS (Îą = 0.55, 95% CI = 0.45-0.64). Additional IHC seems to improve the interobserver agreement of PRGS, particularly between less experienced raters

    Event structures for the reversible early internal pi-calculus

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    The pi-calculus is a widely used process calculus, which models com-munications between processes and allows the passing of communication links.Various operational semantics of the pi-calculus have been proposed, which canbe classified according to whether transitions are unlabelled (so-called reductions)or labelled. With labelled transitions, we can distinguish early and late semantics.The early version allows a process to receive names it already knows from the en-vironment, while the late semantics and reduction semantics do not. All existingreversible versions of the pi-calculus use reduction or late semantics, despite theearly semantics of the (forward-only) pi-calculus being more widely used than thelate. We define piIH, the first reversible early pi-calculus, and give it a denotationalsemantics in terms of reversible bundle event structures. The new calculus is a re-versible form of the internal pi-calculus, which is a subset of the pi-calculus whereevery link sent by an output is private, yielding greater symmetry between inputsand outputs

    Warm‐air advection, air mass transformation and fog causes rapid ice melt

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    Direct observations during intense warm-air advection over the East Siberian Sea reveal a period of rapid sea-ice melt. A semi-stationary, high-pressure system north of the Bering Strait forced northward advection of warm, moist air from the continent. Air-mass transfor-mation over melting sea ice formed a strong, surface-based temperature inversion in which dense fog formed. This induced a positive net longwave radiation at the surface, while reduc-ing net solar radiation only marginally; the inversion also resulted in downward turbulent heat flux. The sum of these processes enhanced the surface energy flux by an average of ~15 W m-2 for a week. Satellite images before and after the episode show sea-ice concentrations decreasing from > 90% to ~50% over a large area affected by the air-mass transformation. We argue that this rapid melt was triggered by the increased heat flux from the atmosphere due to the warm-air advection

    Contribution of sea-ice loss to Arctic amplification is regulated by Pacific Ocean decadal variability

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    The pace of Arctic warming is about double that at lower latitudes – a robust phenomenon known as Arctic amplification (AA)1. Many diverse climate processes and feedbacks cause AA2-7, including positive feedbacks associated with diminished sea ice6,7. However, the precise contribution of sea-ice loss to AA remains uncertain7,8. Through analyses of both observations and model simulations, we show that the contribution of sea-ice loss to wintertime AA appears dependent on the phase of the Pacific Decadal Oscillation (PDO). Our results suggest that for the same pattern and amount of sea-ice loss, consequent Arctic warming is larger during the negative PDO phase, relative to the positive phase, leading to larger reductions in the poleward gradient of tropospheric thickness and to more pronounced reductions in the upper-level westerlies. Given the oscillatory nature of the PDO, this relationship has the potential to increase skill in decadal-scale predictability of Arctic and sub-Arctic climate. Our results indicate that Arctic warming in response to the ongoing long-term sea-ice decline9,10 is greater (reduced) during periods of negative (positive) PDO phase. We speculate that the observed recent shift to the positive PDO phase, if maintained and all other factors being equal, could act to temporarily reduce the pace of wintertime Arctic warming in the near future.J.A.S. was funded by a UK Natural Environment Research Council (NERC) grants NE/J019585/1 and NE/M006123/1. J.A.F. was supported by an NSF/ARCSS grant (1304097) and NASA grant (NNX14AH896). The model simulations were performed on the ARCHER UK National Supercomputing Service. We thank the NOAA ESRL and Met Office Hadley Centre for provision of observational and reanalysis data sets. We also thank D. Ackerley for helping to diagnose the cause of model crashes, C. Deser for commenting on the manuscript prior to submission, and two anonymous reviewers for constructive criticism

    Systemic therapy of Cushing’s syndrome

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    Cushing’s disease (CD) in a stricter sense derives from pathologic adrenocorticotropic hormone (ACTH) secretion usually triggered by micro- or macroadenoma of the pituitary gland. It is, thus, a form of secondary hypercortisolism. In contrast, Cushing’s syndrome (CS) describes the complexity of clinical consequences triggered by excessive cortisol blood levels over extended periods of time irrespective of their origin. CS is a rare disease according to the European orphan regulation affecting not more than 5/10,000 persons in Europe. CD most commonly affects adults aged 20–50 years with a marked female preponderance (1:5 ratio of male vs. female). Patient presentation and clinical symptoms substantially vary depending on duration and plasma levels of cortisol. In 80% of cases CS is ACTH-dependent and in 20% of cases it is ACTH-independent, respectively. Endogenous CS usually is a result of a pituitary tumor. Clinical manifestation of CS, apart from corticotropin-releasing hormone (CRH-), ACTH-, and cortisol-producing (malign and benign) tumors may also be by exogenous glucocorticoid intake. Diagnosis of hypercortisolism (irrespective of its origin) comprises the following: Complete blood count including serum electrolytes, blood sugar etc., urinary free cortisol (UFC) from 24 h-urine sampling and circadian profile of plasma cortisol, plasma ACTH, dehydroepiandrosterone, testosterone itself, and urine steroid profile, Low-Dose-Dexamethasone-Test, High-Dose-Dexamethasone-Test, after endocrine diagnostic tests: magnetic resonance imaging (MRI), ultra-sound, computer tomography (CT) and other localization diagnostics. First-line therapy is trans-sphenoidal surgery (TSS) of the pituitary adenoma (in case of ACTH-producing tumors). In patients not amenable for surgery radiotherapy remains an option. Pharmacological therapy applies when these two options are not amenable or refused. In cases when pharmacological therapy becomes necessary, Pasireotide should be used in first-line in CD. CS patients are at an overall 4-fold higher mortality rate than age- and gender-matched subjects in the general population. The following article describes the most prominent substances used for clinical management of CS and gives a systematic overview of safety profiles, pharmacokinetic (PK)-parameters, and regulatory framework

    The Atmosphere above Ny-Ålesund – Climate and global warming, ozone and surface UV radiation

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    The Arctic region is considered to be most sensitive to climate change, with warming in the Arctic occurring considerably faster than the global average due to several positive feedback mechanisms contributing to the “Arctic amplification”. Also the maritime and mountainous climate of Svalbard has undergone changes during the last decades. Here, the focus is set on the current atmospheric boundary conditions for the marine ecosystem in the Kongsfjorden area, discussed in the frame of long-term climatic observations in the larger regional and hemispheric context. During the last century, a general warming is found with temperature increases and precipitation changes varying in strength. During the last decades, a strong seasonality of the warming is observed in the Kongsfjorden area, with the strongest temperature increase occurring during the winter season. The winter warming is related to observed changes in the net longwave radiation. Moreover, changes in the net shortwave are observed during the summer period, attributed to the decrease in reflected radiation caused by the retreating snow cover. Another related aspect of radiation is the intensity of solar ultra-violet radiation that is closely coupled to the abundance of ozone in the column of air overhead. The long term evolution of ozone losses in the Arctic and their connection to climate change are discussed

    Surface Energy Budgets of Arctic Tundra During Growing Season

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    This study analyzed summer observations of diurnal and seasonal surface energy budgets across several monitoring sites within the Arctic tundra underlain by permafrost. In these areas, latent and sensible heat fluxes have comparable magnitudes, and ground heat flux enters the subsurface during short summer intervals of the growing period, leading to seasonal thaw. The maximum entropy production (MEP) model was tested as an input and parameter parsimonious model of surface heat fluxes for the simulation of energy budgets of these permafrost‐underlain environments. Using net radiation, surface temperature, and a single parameter characterizing the thermal inertia of the heat exchanging surface, the MEP model estimates latent, sensible, and ground heat fluxes that agree closely with observations at five sites for which detailed flux data are available. The MEP potential evapotranspiration model reproduces estimates of the Penman‐Monteith potential evapotranspiration model that requires at least five input meteorological variables (net radiation, ground heat flux, air temperature, air humidity, and wind speed) and empirical parameters of surface resistance. The potential and challenges of MEP model application in sparsely monitored areas of the Arctic are discussed, highlighting the need for accurate measurements and constraints of ground heat flux.Plain Language SummaryGrowing season latent and sensible heat fluxes are nearly equal over the Arctic permafrost tundra regions. Persistent ground heat flux into the subsurface layer leads to seasonal thaw of the top permafrost layer. The maximum energy production model accurately estimates the latent, sensible, and ground heat flux of the surface energy budget of the Arctic permafrost regions.Key PointThe MEP model is parsimonious and well suited to modeling surface energy budget in data‐sparse permafrost environmentsPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150560/1/jgrd55584.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150560/2/jgrd55584_am.pd

    The RISAP-study: a complex intervention in risk communication and shared decision-making in general practice

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    General practitioners (GPs) and patients find it difficult to talk about risk of future disease, especially when patients have asymptomatic conditions, and treatment options are unlikely to cause immediate perceptible improvements in well-being. Further studies in risk communication training are needed. Aim:1) to systematically develop, describe and evaluate a complex intervention comprising a training programme for GPs in risk communication and shared decision-making, 2) to evaluate the effect of the training programme on real-life consultations between GPs and patients with high cholesterol levels, and 3) to evaluate patients' reactions during and after the consultations. Methods/Design The effect of the complex intervention, based around a training programme, will be evaluated in a cluster-randomised controlled trial with an intervention group and an active control group with 40 GPs and 280 patients in each group. The GPs will receive a questionnaire at baseline and after 6 months about attitudes towards risk communication and cholesterol-reducing medication. After each consultation with a participating high cholesterol-patient, the GPs will complete a questionnaire about decision satisfaction (Provider Decision Process Assessment Instrument). The patients will receive a questionnaire at baseline and after 3 and 6 months. It includes questions about adherence to chosen treatment (Morisky Compliance Scale), self-rated health (SF-12), enablement (Patient Enablement Instrument), and risk communication and decision-making effectiveness (COMRADE Scale). Prescriptions, contacts to the health services, and cholesterol level will be drawn from the registers. In each group, 12 consultations will be observed and tape-recorded. The patients from these 24 consultations will be interviewed immediately after the consultation and re-interviewed after 6 months. Eight purposefully selected GPs from the intervention group will be interviewed in a focus group 6 months after participation in the training programme. The process and context of the RISAP-study will be investigated in detail using an action research approach, in order to analyse adaptation of the intervention model to the specific context. Discussion This study aims at providing GPs and patients with a firm basis for active deliberation about preventive treatment options, with a view to optimising adherence to chosen treatment. Trial registration ClinicalTrials.gov Protocol Registration System NCT0118705
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