An epoxy resin, cured with an anhydride, has been modified by the addition of silica nanoparticles. The particles were introduced via a sol–gel technique which gave a very well-dispersed phase of ...nanosilica particles which were about 20
nm in diameter. Atomic force and electron microscopies showed that the nanoparticles were well-dispersed throughout the epoxy matrix. The glass transition temperature was unchanged by the addition of the nanoparticles, but both the modulus and toughness were increased. The measured modulus was compared to theoretical models, and good agreement was found. The fracture energy increased from 100
J/m
2 for the unmodified epoxy polymer to 460
J/m
2 for the epoxy polymer with 13
vol% of nanosilica. The fracture surfaces were inspected using scanning electron and atomic force microscopies, and the results were compared to various toughening mechanisms proposed in the literature. The toughening mechanisms of crack pinning, crack deflection and immobilised polymer were discounted. The microscopy showed evidence of debonding of the nanoparticles and subsequent plastic void growth. A theoretical model of plastic void growth was used to confirm that this mechanism was indeed most likely to be responsible for the increased toughness that was observed due to the presence of the nanoparticles.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Neoadjuvant therapy improves long-term survival after oesophagectomy, treating oesophageal cancer, but the evidence to date is insufficient to determine which of the two main neoadjuvant therapy ...types, chemotherapy (nCT) or chemoradiotherapy (nCRT), is more beneficial. We aimed to compare the effects of nCT with those of nCRT.
This multicentre trial, which was conducted in Sweden and Norway, recruited 181 patients with carcinoma of the oesophagus or the gastro-oesophageal junction who were candidates for curative-intended treatment. The primary end point was histological complete response after neoadjuvant treatment, which has been shown to be correlated with increased long-term survival. Study participants were randomized to nCT or nCRT, followed by surgery with two-field lymphadenectomy. Three cycles of platin/5-fluorouracil were administered in both arms, whereas 40 Gy of concomitant radiotherapy was added in the nCRT arm.
The trial met the primary end point, histological complete response being achieved in 28% after nCRT versus 9% after nCT (P = 0.002). Lymph-node metastases were observed in 62% in the nCT group versus 35% in the nCRT group (P = 0.001). The R0 resection rate was 87% after nCRT and 74% after nCT (P = 0.04). There was no difference in overall survival between the treatment arms.
The addition of radiotherapy to neoadjuvant chemotherapy results in higher histological complete response rate, higher R0 resection rate, and a lower frequency of lymph-node metastases, without significantly affecting survival.
NCT01362127 (https://clinicaltrials.gov; The full study protocol was registered in the Clinical Trials Database).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Infiltrating low-grade gliomas (LGG; WHO grade 2) typically present with seizures in young adults. LGGs grow continuously and usually transform to higher grade of malignancy, eventually causing ...progressive disability and premature death. The effect of up-front surgery has been controversial and the impact of molecular biology on the effect of surgery is unknown. We now present long-term results of upfront surgical resection compared with watchful waiting in light of recently established molecular markers.
Population-based parallel cohorts were followed from two Norwegian university hospitals with different surgical treatment strategies and defined geographical catchment regions. Inregion A watchful waiting was favored while early resection was favored inregion B. Thus, the treatment strategy in individual patients depended on their residential address. The inclusion criteria were histopathological diagnosis of supratentorial LGG from 1998 through 2009 in patients 18 years or older. Follow-up ended 1 January 2016. Making regional comparisons, the primary end-point was overall survival.
A total of 153 patients (66 fromregion A, 87 fromregion B) were included. Early resection was carried out in 19 (29%) patients inregion A compared with 75 (86%) patients inregion B. Overall survival was 5.8 years (95% CI 4.5–7.2) inregion A compared with 14.4 years (95% CI 10.4–18.5) inregion B (P<0.01). The effect of surgical strategy remained after adjustment for molecular markers (P=0.001).
In parallel population-based cohorts of LGGs, early surgical resection resulted in a clinical relevant survival benefit. The effect on survival persisted after adjustment for molecular markers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Thermoplastic/epoxy blends were formed using an amine-cured epoxy polymer and a semi-crystalline thermoplastic: syndiotactic polystyrene (sPS). Complete phase-separation of the initially soluble sPS ...from the epoxy occurred via ‘reaction-induced phase-separation’ (RIPS) or via ‘crystallisation-induced phase-separation’ (CIPS), depending upon the thermal processing history employed. Dynamic mechanical thermal analysis showed that no sPS was retained dissolved in the epoxy polymer. For RIPS, at concentrations of sPS of up to 8
wt%, the sPS is present solely as spherical particles. However, macro phase-separation, giving a co-continuous microstructure, accompanied by local phase-inversion, dominates the RIPS blends containing more than 8
wt% sPS. In the CIPS blends, the sPS is present as spherulitic particles, and this microstructure does not change over the range of sPS concentrations employed, i.e. from 1 to 12
wt% sPS. The pure epoxy polymer was very brittle with a value of fracture energy,
G
Ic, of about 175
J/m
2. However, the addition of the sPS significantly increases the value of
G
Ic, though the toughness of the RIPS and CIPS blends differs markedly. For the RIPS blends, there is a steady increase in the toughness with increasing content of sPS and an apparent maximum value of
G
Ic of about 810
J/m
2 is obtained for 8–10
wt% sPS. On the other hand, the measured toughness of the CIPS blends increases relatively slowly with the concentration of sPS, and a maximum plateau value of only about 350
J/m
2 was measured in the range of 8–12
wt% sPS. The relationships between the microstructure of the RIPS and CIPS sPS/epoxy blends and the measured fracture energies are discussed. Further, from scanning electron microscopy studies of the fracture surfaces and optical microscopy of the damage zone around the crack tip, the nature of the micromechanisms responsible for the increases in toughness of the blends are identified. For the RIPS blends, (i) debonding of the sPS particles, followed by (ii) plastic void growth of the epoxy matrix are the major toughening micromechanisms. The increase in toughness due to such micromechanisms is successfully predicted theoretically using an analytical model. In the case of the CIPS blends, the increase in the value of
G
Ic results from (i) crack deflection and (ii) microcracking and crack bifurcation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Patients with multiple myeloma (MM) suffer from a general impaired immunity comprising deficiencies in humoral responses, T‐cell responses as well as dendritic cell (DC) function. Thus, to achieve ...control of tumour growth through immune therapy constitutes a challenge. Careful evaluation of the immune status in patients with MM seems crucial prior to active immune therapy. We evaluated the proportion of both, DC, Treg cells and myeloid‐derived suppressor cells (MDSC) in peripheral blood from patients with MM at diagnosis and in remission as well as patients with monoclonal gammopathy of undetermined significance (MGUS). We found that the proportion of both myeloid (m) DC and plasmacytoid (p) DC in patients at diagnosis was lowered compared to control donors, while only the proportion of pDC in patients in remission and with MGUS was significantly lower than in controls. The proportion of CD4+FOXP3+ Treg cells was increased in patients at diagnosis and not in patients in remission or with MGUS. Also, Treg cells from patients with MM were functionally intact as they were able to inhibit proliferation of both CD4 and CD8 T cells. Finally, we observed an increase in the proportion of CD14+HLA‐DR⁻/low MDSC in patients with MM at diagnosis, illustrating that this cell fraction is also distorted in patients with MM. Taken together, our results illustrate that, both mDC, pDC, Treg cells and MDSC are affected in patients with MM underlining the fact that the immune system is dysregulated as a consequence of the disease.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
To develop and externally validate prediction models for incident hand osteoarthritis (OA) in a large population-based cohort of middle aged and older men and women.
We included 17,153 men and 18,682 ...women from a population-based cohort, aged 35–70 years at baseline (1995–1997). Incident hand OA were obtained from diagnostic codes in the Norwegian National Patient Register (1995–2018). We studied whether a range of self-reported and clinically measured predictors could predict hand OA, using the Area Under the receiver-operating Curve (AUC) from logistic regression. External validation of an existing prediction model for male hand OA was tested on discrimination in a sample of men. Bootstrapping was used to avoid overfitting.
The model for men showed modest discriminatory ability (AUC = 0.67, 95% CI 0.62–0.71). Adding a genetic risk score did not improve prediction. Similar discrimination was observed in the model for women (AUC = 0.62, 95% CI 0.59–0.64). Prediction was not improved by adding a genetic risk score or hormonal and reproductive factors. Applying external validation, similar results were observed among men in HUNT (The Nord-Trøndelag Health Study) as in the developmental sample (AUC = 0.62, 95% CI 0.57–0.65).
We developed prediction models for incident hand OA in men and women. For women, the model included body mass index (BMI), heavy physical work, high physical activity and perceived poor health. The model showed moderate discrimination. For men, we have shown that a prediction model including BMI, education and information on sleep can predict incident hand OA in several populations with moderate discriminative ability.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Observational studies have suggested that low blood pressure and blood pressure variability may partially explain adverse neurological outcome after endovascular therapy with general anaesthesia (GA) ...for acute ischaemic stroke. The aim of this study was to further examine whether blood pressure related parameters during endovascular therapy are associated with neurological outcome.
The GOLIATH trial randomised 128 patients to either GA or conscious sedation for endovascular therapy in acute ischaemic stroke. The primary outcome was 90 day modified Rankin Score. The haemodynamic protocol aimed at keeping the systolic blood pressure >140 mm Hg and mean blood pressure >70 mm Hg during the procedure. Blood pressure related parameters of interest included 20% reduction in mean blood pressure; mean blood pressure <70 mm Hg, <80 mm Hg, and <90 mm Hg, respectively; time with systolic blood pressure <140 mm Hg; procedural minimum and maximum mean and systolic blood pressure; mean blood pressure at the time of groin puncture; postreperfusion mean blood pressure; blood pressure variability; and use of vasopressors. Sensitivity analyses were performed in the subgroup of reperfused patients.
Procedural average mean and systolic blood pressures were higher in the conscious sedation group (P<0.001). The number of patients with mean blood pressure <70–90 mm Hg and systolic blood pressure <140 mm Hg, blood pressure variability, and use of vasopressors were all higher in the GA group (P<0.001). There was no statistically significant association between any of the examined blood pressure related parameters and the modified Rankin Score in the overall patient population, and in the subgroup of patients with full reperfusion.
We found no statistically significant association between blood pressure related parameters during endovascular therapy and neurological outcome.
NCT 02317237.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Energetic Electron Precipitation (EEP) from the plasma sheet and the radiation belts ionizes the polar lower thermosphere and mesosphere. EEP increases the production of NOx and HOx, which will ...catalytically destroy ozone, an important element of atmospheric dynamics. Therefore, measurement of the latitudinal extent of the precipitation boundaries is important in quantifying the atmospheric effects of the Sun-Earth interaction. This study uses measurements by the Medium Energy Proton Electron Detector (MEPED) of six NOAA/POES and EUMETSAT/METOP satellites from 2004 to 2014 to determine the latitudinal boundaries of EEP and their variability with geomagnetic activity and solar wind drivers. Variation of the boundaries for different electron energies and Magnetic Local Time (MLT) is studied. Regression analyses are applied to determine the best predictor variable based on solar wind parameters and geomagnetic indices. The highest correlation was found for the pressure-corrected Dst index when applying a linear regression model. A model of the equatorward EEP boundary is developed separately for three different energy channels, >43, >114, and >292 keV, and for 3 hour MLT sectors. For >43 keV EEP, 80% of the equatorward boundaries predicted by the model are within ±2.2° cgmlat. The model exhibits a solar cycle bias where it systematically exaggerates the equatorward movement of the EEP region during solar minimum. The highest accuracy of the model is found in periods dominated by corotating interaction regions/high speed solar wind streams. The result will be a key element for constructing a model of EEP variability to be applied in atmosphere climate models.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Increasing paleoclimatic evidence suggests that the Little Ice Age (LIA) was a global climate change event. Understanding the forcings and associated climate system feedbacks of the LIA is made ...difficult by the scarcity of Southern Hemisphere paleoclimate records. We use a new glaciochemical record of a coastal ice core from Mt. Erebus Saddle, Antarctica, to reconstruct atmospheric and oceanic conditions in the Ross Sea sector of Antarctica over the past five centuries. The LIA is identified in stable isotope (δD) and lithophile element records, which respectively demonstrate that the region experienced 1.6 ± 1.4 °C cooler average temperatures prior to 1850 AD than during the last 150 yr and strong (>57 m s−1) prevailing katabatic winds between 1500 and 1800 AD. Al and Ti concentration increases of an order of magnitude (>120 ppb Al) are linked to enhanced aeolian transport of complex silicate minerals and represent the strongest katabatic wind events of the LIA. These events are associated with three 12–30 yr intervals of cooler temperatures at ca. 1690 AD, 1770 AD and 1840 AD. Furthermore, ice core concentrations of the biogenic sulphur species MS− suggest that biological productivity in the Ross Sea polynya was ~80% higher prior to 1875 AD than at any subsequent time. We propose that cooler Antarctic temperatures promoted stronger katabatic winds across the Ross Ice Shelf, resulting in an enlarged Ross Sea polynya during the LIA.
Purpose
Writing an Advance Directive (AD) is often seen as a part of Advance Care Planning (ACP). ADs may include specific preferences regarding future care and treatment and information that ...provides a context for healthcare professionals and relatives in case they have to make decisions for the patient. The aim of this study was to get insight into the content of ADs as completed by patients with advanced cancer who participated in ACP conversations.
Methods
A mixed methods study involving content analysis and descriptive statistics was used to describe the content of completed My Preferences forms, an AD used in the intervention arm of the ACTION trial, testing the effectiveness of the ACTION Respecting Choices ACP intervention.
Results
In total, 33% of 442 patients who received the ACTION RC ACP intervention completed a My Preferences form. Document completion varied per country: 10.4% (United Kingdom), 20.6% (Denmark), 29.2% (Belgium), 41.7% (the Netherlands), 61.3% (Italy) and 63.9% (Slovenia). Content analysis showed that ‘maintaining normal life’ and ‘experiencing meaningful relationships’ were important for patients to live well. Fears and worries mainly concerned disease progression, pain or becoming dependent. Patients hoped for prolongation of life and to be looked after by healthcare professionals. Most patients preferred to be resuscitated and 44% of the patients expressed maximizing comfort as their goal of future care. Most patients preferred ‘home’ as final place of care.
Conclusions
My Preferences forms provide some insights into patients’ perspectives and preferences. However, understanding the reasoning behind preferences requires conversations with patients.
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