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As cutaneous head and neck malignancies are highly prevalent especially in older patients, the risk of surgical complications is substantial in this potentially vulnerable population. The objective of this study was to evaluate the value of geriatric assessment of this population with respect to postoperative complications. Patients were prospectively included in OncoLifeS, a databiobank. Before surgery, patients underwent a geriatric assessment including multiple validated screening tools for frailty, comorbidity, polypharmacy, nutrition, functional status, social support, cognition and psychological status. Postoperatively, complications (Clavien-Dindo ≥ grade II) were registered. Uni- and multivariable logistic regression analyses were performed yielding odds ratios (ORs) and 95% confidence intervals (95%CIs). 151 patients undergoing surgery for cutaneous head and neck malignancies were included in this study (mean age 78.9 years, 73.5% male). In a multivariable analysis, frailty measured by the Geriatric 8 (G8) (OR = 6.34; 95%CI:1.73–23.25) was the strongest independent predictor of postoperative complications, among other predictors such as major treatment intensity (OR = 2.73; 95%CI:1.19–6.26) and general anesthesia (OR = 4.74; 95%CI:1.02–22.17), adjusted for age and sex. Frailty, measured by G8, is the strongest predictor of postoperative complications in patients undergoing surgery for cutaneous head and neck malignancies in addition to treatment intensity and type of anesthesia. Geriatric screening on multiple domains is recommended for patients with cutaneous malignancies undergoing head and neck surgery is recommended, as this population includes old patients and frequently suffers postoperative complications. [ABSTRACT FROM AUTHOR]

• Single modality treatment is preferred for early-stage oropharyngeal squamous cell carcinoma. • Treatments have shown equal survival but different toxicities. • Worldwide attention has been given to improve shared decision-making. • A decision aid was developed to assist in making treatment choices. The aim of this project is to create an interactive online patient decision aid (PDA) for oropharyngeal cancer (OPSCC) patients, eligible for transoral (robotic) surgery with an ultimate goal to assist both physicians and patients in making treatment choices. Following the International Patient Decision Aid Standards, a mixed-methods approach was employed. The study involved semi-structured in-depth interviews with patients and physicians, thinking-out-loud sessions, and study-specific questionnaires. Thematic coding and analysis were conducted on verbatim transcriptions of audio-recorded interviews. The PDA drafts were evaluated by twenty OPSCC survivors and twenty multidisciplinary specialists. Significant revisions were made after phase 1 to enhance readability and reduce text, whilst incorporating videos and graphics. Following all phases, both patients and specialists rated the PDA as comprehensible, feasible, and a valuable addition to regular counseling. This study showcases the development of a PDA for early stage oropharyngeal cancer patients considering surgery and radiotherapy options. The decision aid emphasizes the disparities in short- and long-term side effects between the two treatments. Patients and physicians found the decision aid to be understandable, user-friendly, and helpful for future patients. The PDA is available on https://beslissamen.nl/. [ABSTRACT FROM AUTHOR]

Social network sites (SNSs) provide adolescents with the opportunity to expand their social circle, which is associated with increased social capital. However, the social capital adolescents built depends on the quality of their friendships on SNSs. As no instruments are available to capture the quality of friendships on SNSs, this study designed and validated the Friendship Quality on Social Network Sites questionnaire ( FQSNS-questionnaire) . The questionnaire consists of five dimensions: satisfaction, companionship, help, intimacy, and self-validation. Explorative and confirmative factor analyses were applied on data of 1.695 friendships (i.e., offline-to-online, online-to-offline, and online friendships) gathered from 1.087 adolescents. Results pointed to a five-factor solution, applicable to any kind of friendship on SNSs and reflecting the proposed five dimensions of friendship quality. Multiple group confirmatory factor analyses supported measurement invariance across younger and older adolescents, and across boys and girls, at the levels of equal factor structure and loadings. Cronbach's alphas indicated a good internal consistency of each dimension. Correlation analysis indicated that the dimensions were strongly correlated to each other, which is unsurprising because they reflect the overall friendship quality. Based upon these results, we can conclude that dimensions of friendship quality can validly and reliably be assessed using the FQSNS-questionnaire . [ABSTRACT FROM AUTHOR]

This study examines the prosocial effects of virtual reality (VR) technology on donation behavior, using a 360° video documentary supporting the nongovernmental organization Charity: Water. Previous research has shown how VR can be used as a way to evoke empathy towards other people. There is, however, limited research on how this technology can be used to elicit more donations for charitable organizations. This paper aims to investigate whether the use of an emotion-inducing 360° video in VR leads to higher donation rates. We conducted a between-participants experiment and collected data from 150 young adults (age 18–25). Results reveal how VR – and especially empathy – significantly impacts donation intentions. Although donation intentions were found to be higher after watching the VR video, many participants were skeptical about making an actual donation. Implications and future research regarding the capabilities of VR technology in eliciting donations and resolving donation uncertainty are discussed. • VR experiences can induce the subjective feeling of spatial presence in virtual environments. • Persuasive storytelling in VR can lead to increased empathy with its users. • VR storytelling can positively influence attitudes towards charitable donations. • The Theory of Planned Behavior can predict donation intentions after exposure to VR. • A Mixed Methods approach revealed adolescents' donation motivations. [ABSTRACT FROM AUTHOR]

Measuring the external quantum efficiency (EQE) of a solar cell is a standard method to gain deeper insights into its opto-electrical properties. For the case of crystalline silicon solar cells, the EQE of a solar cell is often used to assess the quality of the emitter and the passivation scheme. However, the standard EQE measurement method employs a monochromator which means that several minutes are typically needed to complete a single measurement. In academic environments this can form a bottleneck in the research output, while in industrial environments with production speeds of at least 1800 wafers/hour EQE measurements cannot be readily used. In this work, we introduce a new patented characterization tool which we call the Fast Optical Measurement System (FOMS). When using the FOMS, it becomes possible to measure the EQE of amorphous and crystalline silicon solar cells about 3 orders of magnitude faster when compared to a conventional monochromatic measurement. This means that a measurement of the full visible/near-infrared (VIS/NIR) spectrum can be done in 1–10 s, without compromising on accuracy. Additionally, the FOMS can also be used to perform ultrafast reflectance/transmittance once further add-ons to the system are implemented. This opens a path to many optical applications, also outside the photovoltaics field, where fast and accurate broadband measurements are needed. [ABSTRACT FROM AUTHOR]

Drawing on a survey conducted among 1743 pupils in 16 Belgian secondary schools, this study applies an extended theory of planned behavior (TPB) to adolescents’ acceptance of friendship requests sent by online strangers on social network sites (SNSs). As demonstrated in the literature, random friending on social networking sites can heavily impact adolescents’ safety online. Results yielded by means of Structural Equation Modeling show that the subjective norm with regard to the acceptance of strangers as SNS friends is the most important predictor, followed by PBC and attitude. Bonding social capital (an individual’s disposal of strong, intimate ties) is negatively associated with attitude and subjective norm, whereas bridging social capital (an individual’s disposal of weak, superficial ties) is positively associated with the three TPB antecedents. [ABSTRACT FROM AUTHOR]

In a Phase 3 prevention trial, the monoclonal antibody combination casirivimab and imdevimab (REGEN-COVTM) administered subcutaneously (SC) prevented symptomatic SARS-CoV-2 infection in asymptomatic adults/adolescents living in the same household as a SARS-CoV-2-infected individual (index case). Individuals with cardiovascular disease (CVD) and/or diabetes are at increased risk of moderate/severe COVID-19. Uninfected individuals ≥12 years, identified ≤96 hours of index case being diagnosed SARS-CoV-2 positive, were randomized 1:1 to REGEN-COV 1200mg SC or placebo. The primary endpoint was the proportion of participants who developed symptomatic infection (COVID-19) during the 28-day efficacy assessment period among those who were SARS-CoV-2 RT-qPCR negative and without evidence of immunity (seronegative) at baseline. A post-hoc analysis assessed efficacy in participants with CVD (including hypertension) and/or diabetes. Overall safety is reported. The study included SARS-CoV-2 RT-qPCR negative participants at baseline (n=2067). There was an 81.4% relative risk reduction (RRR) of symptomatic infection with REGEN-COV in the overall seronegative population (n=1505; Figure 1; Table 1). In participants with CVD (n=332) or diabetes (n=103), the RRRs of developing symptomatic infection with REGEN-COV versus placebo were 54.9% and 69.0%, respectively. Similar results were observed when analyses were performed regardless of baseline serology status. Treatment-emergent adverse events occurring at ≥2% included COVID-19, asymptomatic COVID-19, headache, and injection-site reaction (Table 2). In study participants with CVD and/or diabetes, who are known to be at increased risk of severe disease if infected, treatment with REGEN-COV SC reduced the risk of developing symptomatic SARS-CoV-2 infection, consistent with the overall study results.. [ABSTRACT FROM AUTHOR]

Sexting has received increasing scholarly and media attention. Especially, minors’ engagement in this behaviour is a source of concern. As adolescents are highly sensitive about their image among peers and prone to peer influence, the present study implemented the prototype willingness model in order to assess how perceptions of peers engaging in sexting possibly influence adolescents’ willingness to send sexting messages. A survey was conducted among 217 15- to 19-year-olds. A total of 18% of respondents had engaged in sexting in the 2 months preceding the study. Analyses further revealed that the subjective norm was the strongest predictor of sexting intention, followed by behavioural willingness and attitude towards sexting. Additionally, the more favourable young people evaluated the prototype of a person engaging in sexting and the higher they assessed their similarity with this prototype, the more they were willing to send sexting messages. Differences were also found based on gender, relationship status and need for popularity. [ABSTRACT FROM AUTHOR]

Abstract: The influence of mineral additions and chemical admixtures on the shear thickening flow behaviour of powder type self-compacting concrete (SCC) is studied by means of a wide-gap concentric cylinder rheometer. The Couette inverse problem is treated by means of the integration method in order to derive the flow curve τ(γ̇) from the torque measurements. According to the experimental results, the shear thickening effect is found to be strongly influenced by the addition of the chemical admixture (a polycarboxylate ether based superplasticizer), whereas mineral additions were found to modify the intensity of shear thickening. The limestone, quartzite and fly ash addition used in this research project, respectively increase, unalter and decrease the shear thickening intensity. The powder volume and the available amount of free water proved to have a major impact on the viscosity of the powder type SCC mixes. Increasing the powder volume or decreasing the amount of free water results in an increased viscosity of the SCC mix. [Copyright &y& Elsevier]

Abstract: Due to its different mix composition (e.g. use of superplasticizer, lower water/powder ratio (W/P) and higher paste volume) and its denser microstructure, different mechanisms and magnitudes concerning the time-dependent deformability, i.e. shrinkage and creep, hold for limestone powder type self-compacting concrete (SCC). For this reason, experimental investigations concerning the shrinkage and creep behaviour of 7 limestone powder type SCC mixtures and 1 reference, traditionally vibrated, concrete mixture (TC1) are performed. The water/cement ratio (W/C), cement/powder ratio (C/P), aggregate type and cement type are studied. The experimental data have been used to verify the accuracy of the CEB-FIP Model Code 1990 (MC-90) in terms of long-term deformations. Test results revealed generally higher shrinkage and creep deformations for the SCC mixtures compared with the TC1 mix. However, whereas the shrinkage deformations are underestimated by MC-90 the creep and overall behaviour of the limestone powder type SCC mixtures are rather well predicted by the same model. In order to properly predict the time-dependent behaviour of limestone powder type SCC in cases of concrete structures (highly) sensitive to shrinkage and creep, a modification of the MC-90 in terms of the total shrinkage strain prediction is proposed by the authors. For creep, test results revealed that the MC-90 creep coefficient prediction could remain unmodified for limestone powder type SCC application. [Copyright &y& Elsevier]

Abstract: For powder type self-compacting concrete (SCC) mixes, commonly used in Belgium, a shear thickening (Herschel–Bulkley) flow behaviour of the fresh mixes is quite often observed. A longstanding problem in rheometry is the so-called “Couette inverse problem”, where one tries to derive the flow curve from the torque measurements T(N) in a (wide-gap) concentric cylinder (Couette) rheometer, with T the torque registered at the inner, stationary cylinder and N the rotational velocity of the outer, rotating, cylinder. In this paper, the Couette inverse problem is approached by means of the integration method in order to convert T(N) into for a wide-gap (R o/R i =1.45) concentric cylinder rheometer. The approach consists in the decoupling of the flow resistance and the power-law flow behaviour after exceeding the flow resistance. The integration approach is validated by experimental verification with different powder type SCC mixtures. By means of illustration, the results of one limestone powder type SCC mixture with different superplasticizer contents are shown in this paper. [Copyright &y& Elsevier]

Abstract: Using tumor cell-restricted overexpression of glutathione peroxidase 4 (GPx4), we investigated the contribution of tumor cell eicosanoids to solid tumor growth and malignant progression in two tumor models differing in tumorigenic potential. By lowering cellular lipid hydroperoxide levels, GPx4 inhibits cyclooxygenase (COX) and lipoxygenase (LOX) activities. GPx4 overexpression drastically impeded solid tumor growth of weakly tumorigenic L929 fibrosarcoma cells, whereas B16BL6 melanoma solid tumor growth was unaffected. Yet, GPx4 overexpression did markedly increase the sensitivity of B16BL6 tumors to angio-destructive TNF-α therapy and abolished the metastatic lung colonizing capacity of B16BL6 cells. Furthermore, the GPx4-mediated suppression of tumor cell prostaglandin E2 (PGE2) production impeded the induction of COX-2 expression by the tumor stress conditions hypoxia and inflammation. Thus, our results reflect a PGE2-driven positive feedback loop for COX-2 expression in tumor cells. This was further supported by the restoration of COX-2 induction capacity of GPx4-overexpressing L929 tumor cells when cultured in the presence of exogenous PGE2. Thus, although COX-2 expression and eicosanoid production may be enabled by PGE2 from the tumor microenvironment, our results demonstrate the predominant tumor cell origin of protumoral eicosanoids, promoting solid tumor growth of weakly tumorigenic tumors and malignant progression of strongly tumorigenic tumors. [Copyright &y& Elsevier]

Pancreatic cancer is a rare but fatal form of cancer, the fourth highest in absolute mortality. Known risk factors include obesity, diet, and type 2 diabetes; however, the low incidence rate and interconnection of these factors confound the isolation of individual effects. Here, we use epidemiological analysis of prospective human cohorts and parallel tracking of pancreatic cancer in mice to dissect the effects of obesity, diet, and diabetes on pancreatic cancer. Through longitudinal monitoring and multi-omics analysis in mice, we found distinct effects of protein, sugar, and fat dietary components, with dietary sugars increasing Mad2l1 expression and tumor proliferation. Using epidemiological approaches in humans, we find that dietary sugars give a MAD2L1 genotype-dependent increased susceptibility to pancreatic cancer. The translation of these results to a clinical setting could aid in the identification of the at-risk population for screening and potentially harness dietary modification as a therapeutic measure. • Distinct roles for dietary fat, protein, and sugar on murine pancreatic cancer • Dietary glucose triggers Mad2l1 upregulation and tumor cell proliferation in mice • Gene-diet interaction identifies sugar-MAD2L1 link in human pancreatic cancer • Dietary plant fats were protective in human pancreatic cancer susceptibility Dooley et al. used parallel analysis of a murine pancreatic cancer model and a human prospective cohort to study the interaction of diet and pancreatic cancer. Both systems identify complex effects with different dietary components, converging on a link between dietary sugar and the cell-cycle checkpoint gene MAD2L1. [ABSTRACT FROM AUTHOR]

Although social media offer adolescents new possibilities for emotion regulation, little is known about how adolescents use different platforms to this end. This study adds to the emotion regulation literature and affordances-of-technologies perspective by describing whether and how adolescents use different social media platforms (Facebook, Instagram, Snapchat, Twitter, Tumblr, YouTube, 9Gag, and blogs) for emotion sharing and how technical, social, and contextual factors influence these practices. In-depth interviews with 22 adolescents aged 14 to 18 show that adolescents share emotions on multiple of these platforms. Although the different platforms have similar affordances, their social norms clearly differ and influence adolescents’ online behavior. Facebook statuses, Instagram, and Snapchat are mostly used for sharing positive emotions, if emotions are shared at all. Twitter and Messenger, on the other hand, are also used for sharing negative emotions, albeit for different reasons. [ABSTRACT FROM AUTHOR]

• Phase 1 study assessed monthly casirivimab+imdevimab (CAS+IMD) in uninfected adults • Repeat monthly CAS+IMD (1200 mg subcutaneously [SC]) was well-tolerated, with low immunogenicity • CAS+IMD (1200 mg SC) showed a substantial risk reduction in COVID-19 occurrence A phase 1, double-blind, placebo-controlled trial was conducted to evaluate the safety, tolerability, and exploratory efficacy of repeat monthly doses of subcutaneous (SC) casirivimab and imdevimab (CAS+IMD) in uninfected adult volunteers. Participants were randomized (3:1) to SC CAS+IMD 1200 mg or placebo every 4 weeks for up to six doses. Primary and secondary end points evaluated safety, pharmacokinetics, and immunogenicity. Exploratory efficacy was evaluated by the incidence of COVID-19 or SARS-CoV-2 seroconversion. In total, 969 participants received CAS+IMD. Repeat monthly dosing of SC CAS+IMD led to a 92.4% relative risk reduction in clinically defined COVID-19 compared with placebo (3/729 [0.4%] vs 13/240 [5.4%]; odds ratio 0.07 [95% CI 0.01-0.27]), and a 100% reduction in laboratory-confirmed COVID-19 (0/729 vs 10/240 [4.2%]; odds ratio 0.00). Development of anti-drug antibodies occurred in a small proportion of participants (<5%). No grade ≥3 injection-site reactions (ISRs) or hypersensitivity reactions were reported. Slightly more participants reported treatment-emergent adverse events with CAS+IMD (54.9%) than with placebo (48.3%), a finding that was due to grade 1-2 ISRs. Serious adverse events were rare. No deaths were reported in the 6-month treatment period. Repeat monthly administration of 1200 mg SC CAS+IMD was well-tolerated, demonstrated low immunogenicity, and showed a substantial risk reduction in COVID-19 occurrence. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: The construction of wind farms introduces artificial hard substrates in sandy sediments. As Atlantic cod (Gadus morhua) and pouting (Trisopterus luscus) tend to aggregate in order to feed around these reefs, energy profiling and trophic markers were applied to study their feeding ecology in a wind farm in the Belgian part of the North Sea. The proximate composition (carbohydrates, proteins and lipids) differed significantly between liver and muscle tissue but not between fish species or between their potential prey species. Atlantic cod showed to consume more energy than pouting. The latter had a higher overall energy reserve and can theoretically survive twice as long on the available energy than cod. In autumn, both fish species could survive longer on their energy than in spring. Polyunsaturated fatty acids were found in high concentrations in fish liver. The prey species Jassa and Pisidia were both rich in EPA while Jassa had a higher DHA content than Pisidia. Energy profiling supported the statement that wind farm artificial reefs are suitable feeding ground for both fish species. Sufficient energy levels were recorded and there is no indication of competition. [Copyright &y& Elsevier]

Abstract: We previously described mRNA electroporation as an efficient gene delivery method to introduce tumor-antigens (Ag) into murine immature dendritic cells (DC). Here, we further optimize the protocol and evaluate the capacity of mRNA-electroporated DC as a vaccine for immunotherapy. First, the early DC maturation kinetics and the effect of different lipopolysaccharide incubation periods on the phenotypic maturation profile of DC are determined. Next, we show that either immature or mature DC are equally well electroporated and express and present the transgene at a comparable level after electroporation. We point out that the mRNA electroporation results in a negative effect on the interleukin (IL)-12p70, IL-6, and tumor necrosis factor-α secretion after maturation. Nevertheless, mRNA-electroporated DC induce an effective cytotoxic T lymphocyte (CTL) response in vivo. Mature electroporated DC are significantly more potent in eliciting an Ag-specific CD8+ CTL response compared to their immature electroporated counterparts. In addition, a significant improvement in CTL response is obtained both in the primary and in the memory effector phases when CD4+CD25+ regulatory T cells (Treg) are depleted in vivo prior to immunization. These findings are further substantiated in tumor protection experiments and hold convincing evidence for the merit of Treg cell depletion prior to immunization with mRNA-electroporated DC. [Copyright &y& Elsevier]

Epoxy is a material of choice for demanding applications thanks to its high chemical stability, stiffness, and strength. Yet, its brittle fracture behavior is an important downside for many sectors. Here, we show that the addition of electrospun thermoplastic nanofibers is a viable toughening strategy to design nanofiber reinforced epoxy materials with excellent toughness. Moreover, the use of transparent film-like specimens allowed in-situ imaging during mechanical testing. Optical and scanning electron microscopy, digital image correlation and crack length measurements are used to analyze the toughening mechanisms responsible for high toughening efficiency in detail. The addition of polyamide and polycaprolactone nanofibers resulted in an increased plastic energy uptake up to 100%. In-situ observation of the crack tip showed that the main energy-absorbing mechanism was due to bridging nanofibers. There was a profound decrease in toughening efficiency when nanofibers lacked sufficient adhesion with the matrix only when they were oriented parallel with the crack growth direction. The profound understanding of such underlying mechanisms opens up material design in applications where high toughness is required like adhesives, coatings, and fiber-reinforced composite laminates. Image 1 • Thermoplastic nanofibers provide excellent toughness to brittle epoxy. • Specimen design allows in-situ optical and scanning electron microscopy for analyzing the toughening mechanisms in detail. • Bridging nanofibers behind the crack tip are the main cause of toughness. • Epoxy failure mode becomes more stable when toughened with nanofibers. • The developed method can be utilized to determine nanofiber/matrix adhesion as well. [ABSTRACT FROM AUTHOR]

Most biopharmaceuticals are produced as sterile parenteral preparations, requiring very strict production conditions. In addition, liquid formulations face stability challenges which is why currently around half of all biologics are freeze dried for preservation. The environ- mental impact of the fill and finish processes to produce a freeze dried biopharmaceutical (infliximab) was evaluated from two perspectives: (i) considering only process-specific needs and (ii) calculating the overall site needs. An Exergetic Life Cycle Assessment was conducted using both a bottom-up and top-down approach. The process-specific and overall site needs are 6.5 and 39.6 MJ[sub ex]/vial, respectively. These results reveal that 84% of the cumulative exergy entering the manufacturing plant is non-process-specific. Electricity consumption is the highest footprint driver (86%), dominated by the Heating, Ventilation and Air Conditioning (HVAC) system running during non-production hours and/or supporting non-production related areas. If resource efficiency is pursued, the focal target might need to shift towards non-process-specific needs which are not essential for the product functionality/quality (e.g. full HVAC regime during non-production hours). It should be kept in mind that Good Manufacturing Practices conditions always have to be maintained. Currently performed energy saving measures addressing HVAC systems could potentially reduce the overall site needs calculated in this study by up to 16.5 MJ[sub ex]/vial. [ABSTRACT FROM AUTHOR]

Historical and paleoseismic records in south-central Chile indicate that giant earthquakes on the subduction megathrust – such as in AD1960 ( M w 9.5 ) – reoccur on average every ∼300 yr. Based on geodetic calculations of the interseismic moment accumulation since AD1960, it was postulated that the area already has the potential for a M w 8 earthquake. However, to estimate the probability of such a great earthquake to take place in the short term, one needs to frame this hypothesis within the long-term recurrence pattern of megathrust earthquakes in south-central Chile. Here we present two long lacustrine records, comprising up to 35 earthquake-triggered turbidites over the last 4800 yr. Calibration of turbidite extent with historical earthquake intensity reveals a different macroseismic intensity threshold (≥VII1/2 vs. ≥VI1/2) for the generation of turbidites at the coring sites. The strongest earthquakes (≥VII1/2) have longer recurrence intervals (292 ±93 yrs) than earthquakes with intensity of ≥VI1/2 ( 139 ± 69 yr ). Moreover, distribution fitting and the coefficient of variation (CoV) of inter-event times indicate that the stronger earthquakes recur in a more periodic way (CoV: 0.32 vs. 0.5). Regional correlation of our multi-threshold shaking records with coastal paleoseismic data of complementary nature (tsunami, coseismic subsidence) suggests that the intensity ≥VII1/2 events repeatedly ruptured the same part of the megathrust over a distance of at least ∼300 km and can be assigned to M w ≥ 8.6 . We hypothesize that a zone of high plate locking – identified by geodetic studies and large slip in AD 1960 – acts as a dominant regional asperity, on which elastic strain builds up over several centuries and mostly gets released in quasi-periodic great and giant earthquakes. Our paleo-records indicate that Poissonian recurrence models are inadequate to describe large megathrust earthquake recurrence in south-central Chile. Moreover, they show an enhanced probability for a M w 7.7–8.5 earthquake during the next 110 years whereas the probability for a M w ≥ 8.6 (AD1960-like) earthquake remains low in this period. [ABSTRACT FROM AUTHOR]

The vast majority of studies on parental mediation are quantitative by nature, which leads to a lack of in-depth understanding of how parents define and perform their role as socializing agents in this area. The present study offers new insights into how parental mediation is implemented on a daily basis with regard to adolescents' internet use. Therefore, six focus group interviews with parents of children aged 13 to 17 were performed (in total, 34 participants). Concretely, the study investigated (i) how parents perceive their adolescents' internet use, (ii) how parents define their own role as socializing agents, and (iii) how parents perform internet mediation on a daily basis. The results show that parental mediation is best conceived as a dynamic process that stems from the daily interactions between parents and their adolescent children, rather than as a preconceived set of rules and strategies that are implemented. Open communication and making a connection with the adolescent in terms of his or her internet use are parents' preferred strategies for performing parental mediation. The results have implications in terms of parental mediation research as well as in terms of the support directed at parents of adolescent children. [ABSTRACT FROM AUTHOR]

The East Antarctic Ice Sheet has relatively few field data to constrain its past volume and contribution to global sea-level change since the Last Glacial Maximum. We provide new data on deglaciation history and develop new relative sea-level (RSL) curves along an 80 km transect (from Skallen to Skarsvnes, Langhovde and the Ongul Islands) in Lützow Holm Bay, East Antarctica. The geological constraints were compared with output from two Glacial Isostatic Adjustment (GIA) models. The minimum radiocarbon age for regional deglaciation is c. 11,240 cal. yr BP on West Ongul Island with progressively younger deglaciation ages approaching the main regional ice outflow at Shirase Glacier. Marked regional differences in the magnitude and timing of RSL change were observed. More in particular, in Skarvsnes a minimum marine limit of 32.7 m was inferred, which is c. 12.7 m higher than previously published evidence, and at least 15 m higher than that reported in the other three ice-free areas. Current GIA model predictions slightly underestimate the rate of Late Holocene RSL fall at Skallen, Langhovde, and West Ongul, but provide a reasonable fit to the reconstructed minimum marine limit at these sites. GIA model predictions are unable to provide an explanation for the shape of the reconstructed RSL curve at Skarvsnes. We consider a range of possible explanations for the Skarvsnes RSL data and favour an interpretation where the anomalously high marine limit and rate of RSL fall is due to reactivation of a local fault. [ABSTRACT FROM AUTHOR]

Well-characterised tephra horizons deposited in various sedimentary environments provide a means of synchronising sedimentary archives. The use of tephra as a chronological tool is however still widely underutilised in southern Chile and Argentina. In this study we develop a postglacial tephrochronological model for the Chilean Lake District (ca. 38 to 42°S) by integrating terrestrial and lacustrine records. Tephra deposits preserved in lake sediments record discrete events even if they do not correspond to primary fallout. By combining terrestrial with lacustrine records we obtain the most complete tephrostratigraphic record for the area to date. We present glass geochemical and chronological data for key marker horizons that may be used to synchronise sedimentary archives used for palaeoenvironmental, palaeoclimatological and palaeoseismological purposes. Most volcanoes in the studied segment of the Southern Volcanic Zone, between Llaima and Calbuco, have produced at least one regional marker deposit resulting from a large explosive eruption (magnitude ≥ 4), some of which now have a significantly improved age estimate (e.g., the 10.5 ka Llaima Pumice eruption from Llaima volcano). Others, including several units from Puyehue-Cordón Caulle, are newly described here. We also find tephra related to the Cha1 eruption from Chaitén volcano in lake sediments up to 400 km north from source. Several clear marker horizons are now identified that should help refine age model reconstructions for various sedimentary archives. Our chronological model suggests three distinct phases of eruptive activity impacting the area, with an early-to-mid-Holocene period of relative quiescence. Extending our tephrochronological framework further south into Patagonia will allow a more detailed evaluation of the controls on the occurrence and magnitude of explosive eruptions throughout the postglacial. [ABSTRACT FROM AUTHOR]

The nutritional value of food and its environmental impact have received considerable attention, however an assessment of environmental sustainability of catered meals is lacking. We therefore assessed the nutritional value and resource consumption of a specific catered meal, pork tenderloin with potato croquettes, carrots and mushroom sauce (‘Canteen Pork’). The outcomes are compared with that of an identical meal cooked at home (‘Home’), for which ‘Low’ and ‘High’ scoring hypothetical alternatives were defined (e.g. whether or not frying oil as a waste product was reprocessed or recycled), as well as with that of a vegetarian alternative: Quorn™. The resource consumption impact is assessed from cradle-to-disposal, expressed as the Cumulative Exergy Extraction from the Natural Environment (CEENE). Exergy is the amount of useful energy. The CEENE approach accounts for all resource types and is unique since it considers the deprived natural net primary production (expressed in exergy) as the impact for human land occupation, highly relevant for crop and thus food production. The food production, processing and packaging stage accounts for the largest amount of resource consumption compared to food preparation and waste management. The ‘Home Pork High’ scenario has the highest resource consumption at 83 MJex meal −1 . ‘Home Pork Low’, ‘Home Quorn™ High’, ‘Canteen Pork’, ‘Home Quorn™ Low’ and ‘Canteen Quorn’ have a 15, 18, 26, 32 and 40% lower resource consumption compared to ‘Home Pork High’, respectively. For all scenarios, biomass resources contribute 52–64% of the total CEENE, mainly through land occupation. The nutritional analysis, via nutritional density scoring (the higher the better), resulted in a score of 18.1 and 31.2 for the ‘Home Quorn Low’ and ‘High’, 10.4 and 23.4 for the ‘Home Pork High’ and ‘Low’ scenario and 17.0 and 27.3 for the ‘Canteen Pork’ and ‘Canteen Quorn™’, respectively. To conclude, the vegetarian meal scores best on both attributes, however, this effect diminishes considerably if one considers outcomes per energy or protein amount. With regards to catered vs home cooked meals, resource consumption is lower in canteen prepared meals than in the case of the home-cooked meal. However, the nutritional value can be lower or higher depending on consumer behaviour, namely the extent of the use, type and application of butter is key in altering this result. [ABSTRACT FROM AUTHOR]

Background Autologous monocyte-derived dendritic cells (DCs) electroporated with synthetic messenger RNA (mRNA) encoding a CD40 ligand, a constitutively active Toll-like receptor 4 and CD70, together with mRNA encoding fusion proteins of a human leukocyte antigen (HLA)-class II targeting signal (DC-LAMP) and a melanoma-associated antigen (MAA); either MAGE-A3, MAGE-C2, tyrosinase or gp100) (TriMixDC-MEL) are superiorly immunogenic. Patients and methods In this phase IB clinical trial, 24 million viable DCs were administered by four biweekly combined intradermal (id) and intravenous (iv) administrations, and a fifth administration on week 16. The number of iv-administered DCs was escalated in four sequentially treated cohorts. Immune responses were assessed by analysis of antigen specificity of blood-derived T-cells and skin infiltrating lymphocytes (SKILs). Results Fifteen patients with pretreated advanced melanoma tolerated administration of TriMixDC-MEL well. Two patients achieved a complete response and two patients a partial response. All objective responders are progression-free after a follow-up of, respectively, 24+, 28+, 33+, and 34+ months. Post-therapy antigen-specific SKILs were documented in 6 of 12 patients, and antigen-specific CD8+ T-cells were detected in the blood of 4 of 5 patients. Conclusions Cellular immunotherapy with TriMixDC-MEL is safe and immunogenic. Antitumor activity with durable disease control is observed across the investigated iv-dose levels. ClinicalTrials.gov Identifier NCT01066390. [ABSTRACT FROM PUBLISHER]

It is generally thought that dendritic cells (DCs) loaded with full-length tumor antigen could improve immunotherapy by stimulating broad T-cell responses and by allowing treatment irrespective of the patient's human leukocyte antigen (HLA) type. To investigate this, we determined the specificity of T cells from melanoma patients treated with DCs loaded with mRNA encoding a full-length tumor antigen fused to a signal peptide and an HLA class II sorting signal, allowing presentation in HLA class I and II. In delayed-type hypersensitive (DTH)-biopsies and blood, we found functional CD8+ and CD4+ T cells recognizing novel treatment-antigen-derived epitopes, presented by several HLA types. Additionally, we identified a CD8+ response specific for the signal peptide incorporated to elicit presentation by HLA class II and a CD4+ response specific for the fusion region of the signal peptide and one of the antigens. This demonstrates that the fusion proteins contain newly created immunogenic sequences and provides evidence that ex vivo-generated mRNA-modified DCs can induce effector CD8+ and CD4+ T cells from the naive T-cell repertoire of melanoma patients. Thus, this work provides definitive proof that DCs presenting the full antigenic spectrum of tumor antigens can induce T cells specific for novel epitopes and can be administered to patients irrespective of their HLA type. [ABSTRACT FROM AUTHOR]

Abstract: Based on an experimental programme, including autogenous shrinkage tests on concrete, ultrasonic monitoring of fresh concrete, and mercury intrusion porosimetry, the influence of the filler type on the autogenous shrinkage of self-compacting concrete has been investigated. The onset of percolating structure formation (time zero) is influenced by the filler type due to a possible accelerating effect of the filler on the cement hydration. Limestone filler accelerates the hydration process, and reduces time zero, while this is not the case when using quartzite filler. Using fly ash, showing only a slight acceleration, a slight reduction of time zero is obtained. A very significant swelling peak is noticed during the first day. This swelling peak is not a measuring artefact, but is caused mainly by water absorption on the filler surface and resulting disjoining pressure. Some part of the swelling peak might also be caused by Ca(OH)2 crystallisation. The fineness of the filler is an important factor for this swelling behaviour, although also the nature of the filler seems to have an influence. The superplasticiser also interacts with the fillers, influencing the swelling behaviour. The different filler types used in this study did not lead to significant differences in critical pore diameter of the microstructure. This might explain why no significant differences have been found in final autogenous shrinkage values using the different filler types. [Copyright &y& Elsevier]

Abstract: The limitations of highly active anti-retroviral therapy (HAART) have necessitated the development of alternative therapeutic strategies. One of the approaches that has gained prominence in recent years is therapeutic vaccination. We decided to assess the capacity of mature dendritic cells, derived from blood monocytes of HIV-1 infected patients, to generate functional T-cell responses. For this purpose, we constructed a chimeric mRNA encoding the proteins Tat, Rev and Nef. The TaReNef encoding information was linked to the HLA class II-targeting sequence of DC-LAMP. Broadly directed HIV-specific CD4+ and CD8+ cytotoxic T cells exhibiting a poly-functional cytokine secretion pattern were generated by co-culturing with autologous chimeric mRNA electroporated dendritic cells. Thus, administration of ex vivo generated dendritic cells expressing the early proteins Tat, Rev and Nef might offer a promising approach for therapeutic vaccination in HIV-1 infection. [Copyright &y& Elsevier]

The effectiveness of the dendritic cell (DC) vaccination protocols that are currently in use could be improved by providing the DCs with a more potent maturation signal. We therefore investigated whether the T-cell stimulatory capacity of human monocyte–derived DCs could be increased by co-electroporation with different combinations of CD40L, CD70, and constitutively active toll-like receptor 4 (caTLR4) encoding mRNA. We show that immature DCs electroporated with CD40L and/or caTLR4 mRNA, but not those electroporated with CD70 mRNA, acquire a mature phenotype along with an enhanced secretion of several cytokines/chemokines. Moreover, these DCs are very potent in inducing naive CD4+ T cells to differentiate into interferon-γ (IFN-γ)-secreting type 1 T helper (Th1) cells. Further, we assessed the capacity of the electroporated DCs to activate naive HLA-A2-restricted MelanA-specific CD8+ T cells without the addition of any exogenous cytokines. When all three molecules were combined, a >500-fold increase in MelanA-specific CD8+ T cells was observed when compared with immature DCs, and a >200-fold increase when compared with cytokine cocktail–matured DCs. In correlation, we found a marked increase in cytolytic and IFN-γ/tumor necrosis factor-α (TNF-α) secreting CD8+ T cells. Our data indicate that immature DCs genetically modified to express stimulating molecules can induce tumor antigen-specific T cells in vitro and could prove to be a significant improvement over DCs matured with the methods currently in use.Molecular Therapy (2008) 16 6, 1170–1180 doi:10.1038/mt.2008.77 [ABSTRACT FROM AUTHOR]

The use of tumor antigen-loaded dendritic cells (DC) is one of the most promising approaches to inducing a tumor-specific immune response. We compared electroporation of mRNA to lentiviral transduction for the delivery of tumor antigens to human monocyte-derived and murine bone marrow-derived DC. Both lentiviral transduction and mRNA electroporation induced eGFP expression in on average 81% of human DC. For murine DC, eGFP mRNA electroporation (62%) proved to be more efficient than lentiviral transduction (47%). When we used tNGFR as a transgene we observed lentiviral pseudotransduction that overestimated lentiviral efficiency. Neither gene transfer method had an adverse effect on viability, phenotype, or allostimulatory capacity of either human or murine DC. Yet, the mRNA-electroporated DC showed a reduced production of IL-12p70 compared to their lentivirally transduced and unmodified counterparts. Human Ii80MAGE-A3-modified DC and murine Ii80tOVA-modified DC were able to present antigenic epitopes in the context of MHC class I and class II. Both types of modified murine DC were able to induce OVA-specific cytotoxic T cells in vivo; however, the mRNA-electroporated DC were less potent. Our data indicate that this may be related to their impaired IL-12 production. [Copyright &y& Elsevier]