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Mobile health (mHealth) technologies have the potential to capture dense patient data on the background of real-life behavior. Merck & Co., Inc. (Kenilworth, NJ), in collaboration with Koneksa Health, conducted a phase I clinical trial to validate cardiovascular mHealth technologies for concordance with traditional approaches and to establish sensitivity to detect effects of pharmacological intervention. This two-part study enrolled 18 healthy male subjects. Part I, a 5-day study, compared mHealth measures of heart rate (HR) and blood pressure (BP) to those from traditional methods. Hypotheses of similarity, in the clinic and at home, were tested individually for HR, systolic BP, and diastolic BP, at a 2-sided 0.05 alpha level, with a prespecified criterion for similarity being the percentage differences between the 2 measurements within 15%. Part II, a 7-day, 3-period randomized balanced crossover study, evaluated the mHealth technology's ability to detect effects of bisoprolol and salbutamol. Hypotheses that the changes from baseline in HR were greater in the bisoprolol (reduction in HR) and salbutamol (increase in HR) groups compared with no treatment were tested, at a 1-sided 0.05 alpha level. Linear mixed-effects models, Pearson's correlation coefficients, summary statistics, and exploratory plots were applied to analyze the data. The mHealth measures of HR and BP were demonstrated to be similar to those from traditional methods, and sensitive to changes in cardiovascular parameters induced by bisoprolol and salbutamol.

Introduction 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. Methods 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). Results 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. Conclusion 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.

BackgroundData show that a single dose of casirivimab and imdevimab (REGEN-COV®) is effective in treating hospitalized individuals and outpatients with COVID-19 and in post-exposure prophylaxis. We present results from a phase 1, double-blind, placebo-controlled trial evaluating the safety, tolerability, and efficacy of repeat monthly doses of subcutaneous (SC) REGEN-COV in uninfected adult volunteers who were healthy or had chronic stable medical conditions.MethodsSubjects were randomized (3:1) to SC REGEN-COV 1200 mg or placebo dosed every 4 weeks for up to 6 doses. The primary and secondary endpoints evaluated the safety, pharmacokinetics, and immunogenicity of multiple-dose administration of REGEN-COV. Efficacy was evaluated by the incidence of COVID-19 or SARS-CoV-2 seroconversion.ResultsIn total, 969 subjects were treated. Repeat monthly dosing of SC REGEN-COV led to a 92.4% relative risk reduction in clinically-defined COVID-19 compared to 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 was low (ConclusionsRepeated monthly administration of 1200 mg SC REGEN-COV was well-tolerated with low immunogenicity, and showed a substantial risk reduction in COVID-19 occurrence.(ClinicalTrials.gov identifier, NCT04519437)

Conventionally, branch mispredictions are resolved by flushing wrongly speculated instructions from the reorder buffer and refetching instructions along the correct path. However, a large part of the misspeculated instructions could have reconverged with the correct path and executed correctly. Yet, they are flushed to ensure in-order commit. This inefficiency has been recognized in prior work, which proposes either complex additions to a core to reuse the correctly executed instructions, or less intrusive solutions that only reuse part of the converged instructions. We propose a hardware-software cooperative mechanism to recover correctly executed instructions, avoiding the need to refetch and re-execute them. It combines relatively limited additions to the core architecture with a high reuse of reconverged instructions. Adding the software hints to enable our mechanism is a similar effort as parallelizing an application, which is already necessary to extract high performance from current multicore processors. We evaluate the technique on emerging graph applications and sorting, applications that are known to perform poorly on conventional CPUs, and report an average 29% increase in performance.

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 environmental 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 MJex/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 MJex/vial.

Historic masonry structures are particularly sensitive to differential soil settlements. These settlements may be caused by deformable soil, shallow or inadequate foundation, structural additions in the building and changes in the underground water table due to the large-scale land use change in urban areas. This paper deals with the numerical modeling of a church nave wall subjected to differential settlement caused by a combination of the above factors. The building in question, the church of Saint Jacob in Leuven, has suffered extensive damage caused by centuries-long settlement. A numerical simulation campaign is carried out in order to reproduce and interpret the cracking damage observed in the building. The numerical analyses are based on material and soil property determination, the monitoring of settlement in the church over an extended period of time and soil-structure interaction. A sensitivity study is carried out, focused on the effect of material parameters on the response in terms of settlement magnitude and crack width and extent. Soil consolidation over time is considered through an analytical approach. The numerical results are compared with the in-situ observed damage and with an analytical damage prediction model. The authors acknowledge the funding received by BRAIN.be, Belspo in support of the GEPATAR research project (“GEotechnical and Patrimonial Archives Toolbox for ARchitectural conservation in Belgium” BR/132/A6/Gepatar).

BACKGROUND: Although the biopharmaceutical market grows rapidly, the environmental impacts of biopharmaceutical manufacturing have been hardly evaluated. The aim of the study is to comprehensively assess the environmental sustainability of a biologically‐produced active pharmaceutical ingredient (API) manufacturing process. For this purpose, an exergy analysis and an (exergetic) life cycle assessment were performed using primary (foreground system) and modeled data (background system). Infliximab, a monoclonal antibody, was considered. RESULTS: The fermentation and its raw materials' supply chain was determined to have the highest environmental impact, since the culture media requires chemicals and complex compounds such as animal‐derived materials (ADMs). The total impact per 100 mg of API produced ranged between 18.6 and 101.8 MJₑₓ and 2.0–3.1 kg CO₂‐eq, mainly as a function of the ADMs' source. A comparison of infliximab and ustekinumab, a biopharmaceutical produced without ADMs, showed that eliminating these materials can reduce the cumulative resource consumption of monoclonal antibody manufacturing by up to 7.5 times. The fermentation is the process taking the longest and the heating, ventilation and air conditioning system which support fermentation areas consumes approximately 75% of all plant electricity use. CONCLUSIONS: Culture media nutrients and cleanroom requirements are driving factors in the environmental impact of biological API manufacturing. Obtaining more precise data of the bioprocesses behind these nutrients' supply chain is crucial to corroborating this study's results. © 2019 Society of Chemical Industry

Background REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19). Whether subcutaneous REGEN-COV prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent Covid-19 in persons at high risk for infection because of household exposure to a person with SARS-CoV-2 infection is unknown. Methods We randomly assigned, in a 1:1 ratio, participants (≥12 years of age) who were enrolled within 96 hours after a household contact received a diagnosis of SARS-CoV-2 infection to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection. At the time of randomization, participants were stratified according to the results of the local diagnostic assay for SARS-CoV-2 and according to age. The primary efficacy end point was the development of symptomatic SARS-CoV-2 infection through day 28 in participants who did not have SARS-COV-2 infection (as measured by reverse-transcriptase–quantitative polymerase-chain-reaction assay) or previous immunity (seronegativity). Results Symptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P104 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively). No dose-limiting toxic effects of REGEN-COV were noted. Conclusions Subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Among the participants who became infected, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04452318.)

ImportanceEasy-to-administer antiviral treatments may be used to prevent progression from asymptomatic infection to COVID-19 and to reduce viral carriage.ObjectiveEvaluate the efficacy and safety of subcutaneous casirivimab and imdevimab antibody combination (REGEN-COV) to prevent progression from early asymptomatic SARS-CoV-2 infection to COVID-19.DesignRandomized, double-blind, placebo-controlled, phase 3 study that enrolled asymptomatic close contacts living with a SARS-CoV-2–infected household member (index case). Participants who were SARS-CoV-2 RT-qPCR–positive at baseline were included in the analysis reported here.SettingMulticenter trial conducted at 112 sites in the United States, Romania, and Moldova.ParticipantsAsymptomatic individuals ≥12 years of age were eligible if identified within 96 hours of collection of the index case’s positive SARS-CoV-2 test sample.InterventionsA total of 314 asymptomatic, SARS-CoV-2 RT-qPCR–positive individuals living with an infected household contact were randomized 1:1 to receive a single dose of subcutaneous REGEN-COV 1200mg (n=158) or placebo (n=156).Main Outcome(s) and Measure(s)The primary endpoint was the proportion of participants who developed symptomatic COVID-19 during the 28-day efficacy assessment period. The key secondary efficacy endpoints were the number of weeks of symptomatic SARS-CoV-2 infection and the number of weeks of high viral load (>4 log10 copies/mL). Safety was assessed in all treated participants.ResultsSubcutaneous REGEN-COV 1200mg significantly prevented progression from asymptomatic to symptomatic disease compared with placebo (31.5% relative risk reduction; 29/100 [29.0%] vs 44/104 [42.3%], respectively; P=.0380). REGEN-COV reduced the overall population burden of high–viral load weeks (39.7% reduction vs placebo; 48 vs 82 total weeks; P=.0010) and of symptomatic weeks (45.3% reduction vs placebo; 89.6 vs 170.3 total weeks; P=.0273), the latter corresponding to an approximately 5.6-day reduction in symptom duration per symptomatic participant. Six placebo-treated participants had a COVID-19–related hospitalization or ER visit versus none for those receiving REGEN-COV. The proportion of participants receiving placebo who had ≥1 treatment-emergent adverse events was 48.1% compared with 33.5% for those receiving REGEN-COV, including events related (39.7% vs 25.8%, respectively) or not related (16.0% vs 11.0%, respectively) to COVID-19.Conclusions and RelevanceSubcutaneous REGEN-COV 1200mg prevented progression from asymptomatic SARS-CoV-2 infection to COVID-19, reduced the duration of high viral load and symptoms, and was well tolerated.Trial RegistrationClinicalTrials.gov Identifier, NCT04452318KEY POINTSQuestionCan treatment with the anti–SARS-CoV-2 antibody combination REGEN-COV prevent COVID-19 and reduce viral load when given to recently exposed and asymptomatic individuals?FindingsIn this randomized, double-blind, phase 3 trial, subcutaneously administered REGEN-COV 1200 mg significantly reduced progression of asymptomatic SARS-CoV-2 infection to symptomatic infection (ie, COVID-19) by 31.5% compared with placebo. REGEN-COV also reduced the overall population burden of high viral load weeks (39.7% reduction vs placebo; 48 vs 82 total weeks; P=.0010).MeaningIn the current pandemic, utilization of subcutaneous REGEN-COV prevents progression of early asymptomatic infection to COVID-19 and reduces viral carriage.

Background 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. Methods 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. Results 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). Conclusions 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..

We address the challenge faced in characterizing long-running workloads, namely how to reliably focus the detailed analysis on interesting execution regions. We present a set of tools that allows users to precisely capture any region of interest in program execution, and create a stand-alone executable, called an ELFie, from it. An ELFie starts with the same program state captured at the beginning of the region of interest and then executes natively. With ELFies, there is no fast-forwarding to the region of interest needed or the uncertainty of reaching the region. ELFies can be fed to dynamic program-analysis tools or simulators that work with regular program binaries. Our tool-chain is based on the PinPlay framework and requires no special hardware, operating system changes, recompilation, or re-linking of test programs. This paper describes the design of our ELFie generation tool-chain and the application of ELFies in performance analysis and simulation of regions of interest in popular long-running single and multi-threaded benchmarks.

BACKGROUND: Autologous monocyte-derived mRNA co-electroporated dendritic cells with mRNA encoding CD40 ligand (CD40L), CD70 and a constitutively activated TLR4 (caTLR4) (referred to as TriMixDC-MEL) have anti-tumor activity in advanced melanoma patients. We investigated the safety and activity of adjuvant TriMixDC-MEL in stage III/IV melanoma patients. MATERIALS AND METHODS: Forty-one patients were randomly assigned to treatment with TriMixDC-MEL (n = 21) and standard follow-up (n = 20). "Cross-over" was allowed at the time of non-salvageable recurrence. The primary endpoint was the percentage of patients alive and disease-free at 1-year. For a subset of patients, (formalin-fixed paraffin-embedded), tumor tissue samples were available for mRNA expression profiling and PD-L1 immunohistochemical staining. RESULTS: Baseline characteristics were well balanced. One-year after randomization, 71% of patients in the study arm were alive and free of disease compared to 35% in the control arm. After a median follow-up of 53 months (range 3-67), 23 patients experienced a non-salvageable melanoma recurrence (TriMixDC-Mel arm n = 9 and control arm n = 14).The median time to non-salvageable recurrence was superior in the TriMixDC-MEL arm (median 8 months (range 1-6) vs. not reached; log-rank p 0.044). TriMixDC-MEL-related adverse events (AE) consisted of transient local skin reactions, flu-like symptoms and post-infusion chills. No grade ≥ 3 AE's occurred. The mRNA expression profiling revealed four genes (STAT2, TPSAB1, CD9 and CSF2) as potential predictive biomarkers. CONCLUSION: TriMixDC-MEL id/iv as adjuvant therapy is tolerable and may improve the 1-year disease-free survival rate. Combination of optimized autologous monocyte-derived DC-formulations warrants further investigation in combination with currently approved adjuvant therapy options.

Summary 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., Graphical Abstract, Highlights • 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.

Improved understanding of cancer immunology has provided insight into the phenomenon of frequent tumor recurrence after initially successful immunotherapy. A delicate balance exists between the capacity of the immune system to control tumor growth and various resistance mechanisms that arise to avoid or even counteract the host's immune system. These resistance mechanisms include but are not limited to (i) adaptive expression of inhibitory checkpoint molecules in response to the proinflammatory environment and (ii) amplification of cancer stem cells, a small fraction of tumor cells possessing the capacity for self-renewal and mediating treatment resistance and formation of metastases after long periods of clinical remission. Several individual therapeutic agents have so far been developed to revert T-cell exhaustion or disrupt the cross-talk between cancer stem cells and the tumor-promoting microenvironment. Here, we demonstrate that a three-arm combination therapy-consisting of an mRNA-based vaccine to induce antigen-specific T-cell responses, monoclonal antibodies blocking inhibitory checkpoint molecules (PD-1, TIM-3, LAG-3), and antibodies targeting IL-6 and TGF-β-improves the therapeutic outcome in subcutaneous TC-1 tumors and significantly prolongs survival of treated mice. Our findings point to a need for a rational development of multidimensional anticancer therapies, aiming at the induction of tumor-specific immunity and simultaneously targeting multiple resistance mechanisms.

We find that another of our outstanding EMC contributors for many decades has passed on. Dr. Tom Dvorak, as I would like to say, was father of the enormously successful EMC Zurich symposium held in several venues but mostly in Zurich, Switzerland. I recall all the times I attended this symposium, giving papers and workshops and chatting with Tom. This allowed me to get to know him better. As will be reported by Gabriel Meyer, his close colleague at ETH in Zurich (Swiss Federal institute), Tom was a stickler for having no less than the “perfect paper” published in the proceedings. This included not only assurance that the technical discussion made sense but also that the physical layout of the paper on paper was perfect. An example of the latter attention to detail was that each column in a two column format on the page had to be identical. In this way, at the bottom of the page, the last line in column 1 was at the same “elevation” as the last line in column 2. To emphasize this point one year, all speakers got a “kit” with scissors, tape, a ruler, and other utensils to make the last lines in each column the same distance from the bottom of the page. I still have that kit. Every time I see it, I recall Tom fondly as the near perfectionist. The tributes to Tom which appear below are from his closest colleagues. Normally I would focus only on the tributes to Tom related to his career. But the stories of his colleagues are as compelling as a history of EMC in Europe; I have extended the material in each tribute. As you will see, the disapproval of Tom's request for having the IEEE International Symposium on EMC in Montreux, Switzerland in 1975 led to his moving ahead with the symposium in Montreux. That spawned the multiyear EMC symposia primarily in Zurich, Switzerland — a real success story. The photo below was taken of Tom at the Zurich EMC Symposium banquet in the Dolder Grande Hotel. I had the pleasure of being there and applauding him for all he did for the symposium. In any case, we now announce with sadness Tom's obituary.

As we think about the good time we had at the 2019 IEEE International Symposium on EMC+SIPI held in New Orleans at the end of July, it is good to remember the increased standards presentations, committee meetings and tutorials held during the symposium week this year.

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.

Vinaya rules are stipulations and advice that guide the Buddhist community (saṃgha) of monks and nuns. They are generally considered to be the basis of monastic life. Without these rules, there is no saṃgha; and without the saṃgha, so it is said, there is no dharma (doctrine). While the rules are attributed to the Buddha, it is clear that they developed over time, influenced by the continuous spread of the Buddhist community throughout the Indian subcontinent in the centuries following the Buddha’s demise. Different traditions gradually arose, each with its own set of vinaya rules. These rules display many similarities, but also differ in some significant respects. With the spread of the Buddhist saṃgha in South, Southeast, and East Asia in the first centuries ce, new guidelines were added to the traditional Indian vinaya rules. Although these rules have their own identifying terms—such as “bodhisattva rules” or “rules of purity”—they are often also designated by the term “vinaya,” in modern times used as a concept that encompasses all monastic, and sometimes even lay, Buddhist guidelines. In addition, many manuals and commentaries were written, adding further guiding principles. When written by very inspirational masters, these commentaries sometimes superseded the original vinaya guidelines. This phenomenon led to greater regional interpretation of how vinaya ought to be understood.

It is common nowadays for parents to share information about their children on social network sites (SNSs). However, little is known on how adolescents think and feel about this sharenting behavior. Therefore, this study explores adolescents' perception of the reasons why parents share information about their adolescent children on SNSs, and adolescents' attitudes toward sharenting. A survey study was conducted among 817 adolescents. Factor analyses pointed toward four perceived sharenting motives: parental advice motives, social motives, impression management motives, and informative-archiving motives. Adolescents believed that parents mainly shared information about their children due to informative-archiving motives. They believed that parental advice motives were less common. Preliminary analyses pointed out that adolescents largely disapproved of sharenting. They mainly considered it as embarrassing and useless. Regression analysis indicated that when adolescents perceived sharenting as an impression management issue, the more negative their attitudes were toward sharenting. Conversely, the more adolescents thought that parents shared information about their children due to informative-archiving motives, the less they disapproved of sharenting. Additionally, when adolescents themselves disclosed more personal information or when they were more often confronted with sharenting, they had more positive attitudes toward sharenting. Adolescents who were more concerned about their online privacy, were more likely to disapprove of sharenting.

Background: HIV therapeutic vaccination aims to improve the immune responses against HIV in order to control viral replication without the need for combined antiretroviral therapy (cART). iHIVARNA-01 is a novel vaccine combining mRNA delivery and T-cell immunogen (HTI) based on conserved targets of effective antiviral T-cell responses. In addition, it holds adequate stimuli required for activating antigen presenting cells (APC)s and co-activating specific T-cells (TriMix), including human CD40L, constitutively active TLR4 (caTLR4) and CD70. We propose that in-vivo targeting of dendritic cells (DCs) by direct administration of a HIV mRNA encoding these immune modulating proteins might be an attractive alternative to target DCs in vitro.Methods/design: This is a phase-IIa, randomized, double-blinded, placebo-controlled, multicenter study in chronically HIV-1 infected patients under stable cART. One of the three study arms is randomly allocated to subjects. Three vaccinations with either HIVACAT T-cell immunogen (HTI)-TriMix (iHIVARNA-01), TriMix or water for injection (WFI) (weeks 0, 2 and 4) are administered by intranodal injection in the inguinal region. Two weeks after the last immunization (week 6) cART is stopped for 12 weeks. The two primary endpoints are: (1) safety and tolerability of intranodal iHIVARNA-01 vaccination compared with TriMix or WFI and (2) induced immunogenicity, i.e., increase in the frequency of HIV-specific T-cell responses between baseline, week 6 and 12 weeks after treatment interruption in iHIVARNA-01-treated patients as compared to the control groups, immunized with TriMix-mRNA or WFI measured by an IFNγ ELISPOT assay. Secondary endpoints include the evaluation of time to viral rebound, plasma viral load (pVL) at w18, the proportion of patients with control of viral load, induction of T-cell responses to new HIV epitopes, polyfunctionality of HIV-specific T-cells, CD8+ T-cell in-vitro HIV suppressive capacity, the effect on viral reservoir (measured by proviral DNA and cell-associated RNA), assessment of viral immune escape by mutation and mRNA expression profiles of host immune genes.Discussion: This trial aims to direct target DC in situ with mRNA encoding HTI and TriMix for co-stimulation. Intranodal injection circumvents laborious DC isolation and handling in the laboratory. The trial extends on the safety results of a phase-I dose-escalating trial. This candidate vaccine could complement or even replace cART for chronic HIV infection and could be applicable to improve the care and cost of HIV infection.Trial registration: EudraCT 2016-002724-83 (22 September 2016); ClinicalTrials.gov, ID: NCT02888756. Registered on 23 August 2016.

A profound comprehension of the nanostructure of hydrogenated amorphous silicon (a-Si:H) and the defect states in this material is currently still lacking despite several decades of research on this topic. Investigating the nature of defects in a-Si:H devices is especially important in view of the poorly understood Staebler–Wronski effect (SWE). Therefore we present the latest insights into the gap states in the a-Si:H bandgap by manipulating these sub gap states in three different ways: via the application of a voltage bias, via in situ light soaking, and via in situ annealing. To monitor the changes in the sub gap absorption we employ an advanced application of Fourier Transform Photocurrent Spectroscopy (FTPS). A recently published optical model that removes interference fringes from the photocurrent spectrum is presented to obtain the absorption coefficient. For FTPS measurements on solar cells the photocurrent spectrum is scaled to the external quantum efficiency (EQE) of the solar cell. Further, a mathematical data fitting routine is employed to accurately quantify the sub gap absorption and the changes therein during light soaking and annealing. The high sensitivity of FTPS is particularly helpful in identifying the sub gap states that play a role in the SWE in a-Si:H devices.

One of the most visible identity markers of Buddhist monasticism is clothing. The robes of monks and nuns have been paid considerable attention by researchers. By contrast, other pieces of monastic clothing have attracted far less attention, and this is particularly the case with footwear. Although shoes certainly play a secondary role compared to robes, they still present the monastic community with a number of complex issues. Shoes touch the ground, so they inevitably get dirty. Hence, wearing shoes could be considered disrespectful when meeting someone or paying homage, but so could showing one’s naked feet. Meanwhile, shoes protect the feet from dirt and injury on difficult roads, so they may be viewed as essential attire. Additional issues relate to the material and the shape of the footwear, and which shoes are the most appropriate in various situations. This study discusses early Buddhist disciplinary (vinaya) texts’ guidelines on issues relating to footwear, and explores how these guidelines were ...

We formerly demonstrated that vaccination with Wilms tumor 1 (WT1)-loaded autologous monocyte-derived dendritic cells (mo-DCs) can be a well-tolerated effective treatment in acute myeloid leukemia (AML) patients. Here, we investigated whether we could introduce the receptor for hyaluronic acid-mediated motility (RHAMM/HMMR/CD168), another clinically relevant tumor-associated antigen, into these mo-DCs through mRNA electroporation and elicit RHAMM-specific immune responses. While RHAMM mRNA electroporation significantly increased RHAMM protein expression by mo-DCs, our data indicate that classical mo-DCs already express and present RHAMM at sufficient levels to activate RHAMM-specific T cells, regardless of electroporation. Moreover, we found that RHAMM-specific T cells are present at vaccination sites in AML patients. Our findings implicate that we and others who are using classical mo-DCs for cancer immunotherapy are already vaccinating against RHAMM.

The effects of a pharmaceutical treatment have until now been evaluated by the field of Health Economics on the patient health benefits, expressed in Quality-Adjusted Life Years (QALYs) versus the monetary costs. However, there is also a Human Health burden associated with this process, resulting from emissions that originate from the pharmaceutical production processes, Use Phase and End of Life (EoL) disposal of the medicine. This Human Health burden is evaluated by the research field of Life Cycle Assessment (LCA) and expressed in Disability-Adjusted Life Years (DALYs), a metric similar to the QALY. The need for a new framework presents itself in which both the positive and negative health effects of a pharmaceutical treatment are integrated into a net Human Health effect. To do so, this article reviews the methodologies of both Health Economics and the area of protection Human Health of the LCA methodology and proposes a conceptual framework on which to base an integration of both health effects. Methodological issues such as the inclusion of future costs and benefits, discounting and age weighting are discussed. It is suggested to use the structure of an LCA as a backbone to cover all methodological challenges involved in the integration. The possibility of monetizing both Human Health benefits and burdens is explored. The suggested approach covers the main methodological aspects that should be considered in an integrated assessment of the health effects of a pharmaceutical treatment.

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.

Objective: The efficacy of therapeutic vaccines against HIV-1 infection has been modest, New inerts to redirect responses to vulnerable sites are urgently needed to improve these results. Design: We performed the first-in-human clinical trial with naked mRNA (IFIIVARNA) combining a dendritic cell activation strategy (TriMix:CD40L+CD70+caTLR4 RNA) with a novel HIV immunogen sequences (HTI immunogen). Methods: A dose escalation, phase I clinical trial was performed in 21 chronic HIV-1-infected patients under ART who received three intranodal doses of mRNA (weeks 0, 2 and 4) as follow: TriMix-100g, TriMix-300g, TriMix-300g with HTI 300g, TriMix-300 g with HTI-600g, TriMix-300g with HTI-900g. Primary end-point was safety and secondary exploratory end-points were immunogenicity, changes in viral reservoir and transcriptome. Results: Overall, the vaccine was secure and well tolerated. There were 31 grade 1/2 and 1 grade 3 adverse events, mostly unrelated to the vaccination. Patients who received the highest dose showed a moderate increase in T-cell responses spanning HTI sequence at week 8, In addition, the proportion of responders receiving any dose of HTI increased from 31% at w0 to 80% postvaccination. The intervention had no impact on caHIV-DNA levels, however, cal-IIV-RNA expression and usVL were transiently increased at weeks 5 and 6 in the highest dose of iHIVARNA, and these changes were positively correlated with HIV-1-specific-induced immune responses. Conclusion: This phase I dose-escalating trial showed that iHIVARNA administration was safe and well tolerated, induced moderate HIV-specific T-cell responses and transiently increased different viral replication readouts. These data support further exploration of iHIVARNA in a phase II study. Copyright (C) 2018 The Authon(s). Published by Wolters Kluwer Health, Inc.

Background Mass anthelmintic drug administration is recommended in developing countries to address infection by soil-transmitted helminthiases (STH). We quantified the public health benefit of treatment with mebendazole in eight million Vietnamese children aged 5–14 years from 2006 to 2011. This was compared to the environmental impact of the pharmaceutical supply chain of mebendazole, as the resource use and emissions associated with pharmaceutical production can be associated with a public health burden, e.g. through emissions of fine particulate matter. Methodology Through Markov modelling the disability due to STH was quantified for hookworm, Ascaris lumbricoides and Trichuris trichiura. For each worm type, four levels of intensity of infection were included: none, light, medium and heavy. The treatment effect on patients was quantified in Disability-Adjusted Life Years (DALYs). The public health burden induced by the pharmaceutical supply chain of mebendazole was quantified in DALYs through Life Cycle Assessment. Principal findings Compared to ‘no treatment’, the modelled results of five-year treatment averted 116,587 DALYs (68% reduction) for the three worms combined and largely driven by A. lumbricoides. The main change in DALYs occurred in the first year of treatment, after which the results stabilized. The public health burden associated with the pharmaceutical supply chain was 6 DALYs. Conclusions The public health benefit of the Mass Drug Administration (MDA) averted substantially more DALYs than those induced by the pharmaceutical supply chain. These results were verified in a sensitivity analysis. The starting prevalence for each worm was the most sensitive model parameter. This methodology is useful for policymakers interested in a holistic approach towards the public health performance of MDA programs, enveloping both the treatment benefit received by the patient and the public health burden associated with the resource consumption and environmental emissions of the pharmaceutical production and supply chain., Author summary Millions of children from developing countries are infected by soil-transmitted helminthiases (STH), an infection of intestinal worms that cause abdominal pain, bad absorption of nutrients from food and a decrease in the amount of red blood cells. This disease can be treated with anthelmintic medication, such as mebendazole, that decreases the intensity of infection and leads to a public health benefit. Because reinfection often occurs within months, regular treatment (every six months) is advised. Given the number of people that are infected with this disease, numerous tablets are required each year to facilitate treatment. However, the industrial production of these tablets can have a negative effect on global human health, e.g. through emissions of fine particulate matter, which should be considered as a public health burden. Our findings suggest that the public health benefit of treating STH with anthelmintic medication is 18,035 times larger than the public health burden associated with pharmaceutical production. However, the conclusion that the health benefits for the patients outweigh the health damage due to resource use and emission from industry may not hold for every medical treatment, therefore we propose a more holistic evaluation of health care programmes, including a broader approach towards human health.

In modern processors, prefetching is an essential component for hiding long-latency memory accesses. However, prefetching too aggressively can easily degrade performance by evicting useful data from cache, or by saturating precious memory bandwidth. Tuning the prefetcher's activity is thus an important problem. Existing techniques tend to focus on detecting negative symptoms of aggressive prefetching, such as unused prefetches being evicted or memory bandwidth saturation, and throttle the prefetcher in response. We argue that these far-side throttling techniques are inefficient because they require significant tracking state, and are reactive to negative effects rather than being proactive. We propose an alternative technique which we coin near-side throttling, which works by detecting late prefetches and tuning the prefetch distance to closely track the point at which most prefetches are not late. Because late prefetches are by definition useful, detecting late prefetches exclusively suffices to detect and prevent useless prefetches as well. Our solution is cheap to implement in hardware, includes throttling on off-chip bandwidth saturation, applies to both hardware and software prefetching, and can control multiple concurrent prefetchers where it will naturally allow the most useful prefetch algorithm to generate most of the requests. Through detailed simulation of a many-core architecture running a wide range of sequential and parallel applications, we show that our near-side throttling (NST) proposal performs similar to the state-of-the-art feedback-directed prefetching (FDP), even though it has a significantly lower implementation cost, can react more quickly to changes in application behavior and is applicable to a more varied set of use cases.

AIMS/HYPOTHESIS: The initial avascular period following islet transplantation seriously compromises graft function and survival. Enhancing graft revascularisation to improve engraftment has been attempted through virus-based delivery of angiogenic triggers, but risks associated with viral vectors have hampered clinical translation. In vitro transcribed mRNA transfection circumvents these risks and may be used for improving islet engraftment. METHODS: Mouse and human pancreatic islet cells were transfected with mRNA encoding the angiogenic growth factor vascular endothelial growth factor A (VEGF-A) before transplantation under the kidney capsule in mice. RESULTS: At day 7 post transplantation, revascularisation of grafts transfected with Vegf-A (also known as Vegfa) mRNA was significantly higher compared with non-transfected or Gfp mRNA-transfected controls in mouse islet grafts (2.11- and 1.87-fold, respectively) (vessel area/graft area, mean ± SEM: 0.118 ± 0.01 [n = 3] in Vegf-A mRNA transfected group (VEGF) vs 0.056 ± 0.01 [n = 3] in no RNA [p

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. (C) 2018 Elsevier Ltd. All rights reserved.

The American National Standards Institute Accredited Standards Committee C63® (EMC) took its continuing major annual workshops this time to the Bayou. This workshop, which was focused on compliance testing of wireless devices, licensed and unlicensed, was held on July 20. This was the Saturday before the start of the 2019 IEEE International Symposium on EMC+SIPI held in New Orleans, Louisiana. The ANSI C63 standards specifically addressed in the workshop included: • C63.10 "American National Standard for testing unlicensed wireless devices" covering measurements of emissions from such transmitters • C63.26 "American National Standard of procedures for compliance testing of transmitters used in licensed radio services" covering measurement of emissions from these transmitters.

SEPA (Smart Electric Power Alliance) is a not for profit organization that is working for grid modernization including efficient energy use of communication technologies superimposed on the grid between the power generation point and customer locations using power. In the past three years, SEPA has published four "whitepapers" examining the need for EMC to be considered for devices installed on the power grid as well as other critical locations such as that at a power substation.

Study Objective: To evaluate next-morning driving performance in adults younger than 65 years, after single and repeated doses of suvorexant 20 and 40 mg. Design: Double-blind, placebo-controlled, 4-period crossover study. Setting: Maastricht University, The Netherlands. Participants: 28 healthy volunteers (15 females), aged 23 to 64 years. Interventions: Suvorexant (20 and 40 mg) for 8 consecutive nights; zopiclone 7.5 mg nightly on day 1 and 8; placebo. Measurements: Performance on day 2 and 9 (9 h after dosing) using a one-hour standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug-placebo changes in SDLP > 2.4 cm were considered to reflect meaningful driving impairment. Results: Mean drug-placebo changes in SDLP following suvorexant 20 and 40 mg were 1.01 and 1.66 cm on day 2, and 0.48 and 1.31 cm on Day 9, respectively. The 90% CIs of these changes were all below 2.4 cm. Symmetry analysis showed that more subjects had SDLP changes > 2.4 cm than < -2.4 cm following suvorexant 20 and 40 mg on day 2, and following suvorexant 40 mg on day 9. Four female subjects requested that a total of 5 driving tests-all following suvorexant-stop prematurely due to self-reported somnolence. Conclusions: As assessed by mean changes in standard deviation of lateral position (SDLP), there was no clinically meaningful residual effect of suvorexant in doses of 20 and 40 mg on next-morning driving (9 h after bedtime dosing) in healthy subjects < 65 years old. There may be some individuals who experience next-day effects, as suggested by individual changes in SDLP and prematurely stopped tests.

Towards the end of the nineteenth century and the beginning of the twentieth century new technological evolutions and material developments gave rise to different modular structural flooring systems, which allowed light but strong floors to be constructed. This paper gives an overview of the evolution in flooring systems, their durability problems, and how to solve them. Similar systems also have been used for roof constructions. The strengthening of an atypical vaulted roof structure in the “Het Depot” theatre in Leuven, composed of terracotta arch and panel elements, showing its specific problematic and its specific revalorization approach serves as a case study to illustrate the methodologies applied.

Objectives: We sought to validate Cognitive Research Corporation’s Driving Simulator (CRCDS Mini-Sim) for studies of drug safety with respect to driving ability. Methods: A total of 30 healthy subjects were randomized to receive placebo or 7.5 mg zopiclone, a hypnotic known to impair driving, in random order during the 2 treatment periods of a 2 period crossover design. Results: Evening administration of 7.5 mg zopiclone increased next-day standard deviation of lateral lane position (SDLP) by 2.62 cm on average compared with evening administration of placebo, and caused significant effects on symmetry analysis. The magnitude of the change in SDLP is highly similar to changes previously observed using on-the-road driving methods. Conclusions: Further validation of the CRCDS Mini-Sim is warranted to develop this platform for drug safety studies.

The last meeting in 2015 of ACEC was held in Boston on 17 and 18 November. The venue was close to the IEC (International Electrotechnical Commission) North American office in Worcester, Massachusetts. Fourteen of the 18 members were in attendance at the meeting chaired by Don Heirman (Don HEIR-MAN Consultants). They traveled from Europe, Japan, China, and both coasts of the US.

The EMC Society has suffered losses of three major contributors to our EMC discipline. One was a part of the founding members of the Society and two were major contributors to the application of EMC principles. I am saddened to report that Sam Burruano, who was one of the founders of the EMC Society which was called the Professional Group on RFI back at the start in 1957, has passed way. In the same time period, “Bud” Hoeft, who contributed much in the area of connector and cable shielding and its application to shielding of aircraft also passed as did Dave Hanttula who first practiced EMC at a startup company called “Apple”.

Background Environmental impact assessments of pharmaceuticals typically consider only a part of the pharmaceutical supply chain, e.g. tablet formulation. While the environmental impact can be expressed in environmental Human Health burden due to resource use and emissions, the Human Health benefit of the pharmaceutical treatment of patients is currently not simultaneously taken into account. The study aims include a cradle-to-grave assessment of all Human Health impacts of the production, administration and disposal of two antipsychotics for the treatment of schizophrenia. This is complemented with the environmental impact of health care providers such as hospitals. The aim is to holistically quantify to what extent the environmental Human Health burden compares to the Human Health benefit associated with the treatment. Methods We applied an overall framework which included Life Cycle Assessment to model the environmental Human Health impacts of the pharmaceutical supply chain, administration and disposal of the drug and health care providers. To model the patient benefit, this was complemented with a Markov model with a 1-year time horizon. Three patient groups were modeled: medicine coverage of paliperidone palmitate for either one month (PP1M) or three months (PP3M) at a time, and compared to Treatment Interruption (TI) as a control group. Outcomes were quantified using Years of Life Lost (YLL), Years Lived with Disability (YLD) and Disability-Adjusted Life Years (DALY). Results The main environmental impacts were visits to the psychiatrist and psychiatric hospitals. The pharmaceutical supply chain had a limited impact. For 1000 patients for 1 year, PP1M and PP3M respectively avoided 0.38 and 0.49 environmental DALYs compared to TI. PP1M and PP3M further avoided 45.60 and 57.87 YLL and 23.31 and 29.91 YLD compared to TI. The main outcome was the sum of environmental DALYs, YLL and YLD, in which PP1M and PP3M respectively avoided 69.29 and 88.26 DALYs. Alternative analysis of Quality-Adjusted Life Years confirmed the results. Conclusions The overall environmental burden was lower for PP1M and PP3M treatment than Treatment Interruption because patients are kept more stable, which reduces the environmental burden due to hospitals. Moreover, the Human Health burden was outweighed by the Human Health benefit. Electronic supplementary material The online version of this article (10.1186/s12913-019-4247-2) contains supplementary material, which is available to authorized users.

▪ Check instrumentation calibration ▪ Improve test standard EUT setup details and check test site validation ▪ Repeat test and EUT maximization response ▪ Participate in inter-laboratory comparisons and/or proficiency training ▪ Take into account measurement uncertainty in terms of adequate margin

Electromagnetic Interoperability Issues Working Group — Continues to raise awareness for the need to incorporate EMC guidance and standards into the design of the Smart Grid — Working to include EMC into the testing and certifications process for Smart Grid systems.

Vitamin D has been proposed as a therapeutic strategy in pancreatic cancer, yet evidence for an effect of dietary vitamin D on pancreatic cancer is ambiguous, with conflicting data from human epidemiological and intervention studies. Here, we tested the role of dietary vitamin D in the in vivo context of the well-characterized Ela1-TAg transgenic mouse model of pancreatic acinar cell carcinoma. Through longitudinal magnetic resonance imaging of mice under conditions of either dietary vitamin D deficiency (

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. Parents' perceived role regarding internet parenting defines what practices are applied.Parents' mediation practices are dynamic and alter in response to the child's internet use.Rule-setting and limiting the internet use are perceived as negative mediation practices.Parents prefer open communication and connecting with their child as mediation strategies.

PURPOSE: Melanoma patients with a high risk of recurrence may benefit from immunotherapy with mRNA-electroporated autologous monocyte-derived dendritic cells (DCs). Further benefit may be found in combining DC-therapy with interferon alfa-2b. PATIENTS AND METHODS: The long-term clinical outcome of AJCC stage III/IV melanoma patients who had no evidence of disease at the time of treatment with autologous mRNA-electroporated DCs in a single-center pilot clinical trial was analyzed. Antigen loading was accomplished by co-electroporation of mRNA encoding a fusion protein between MAGE-A1, -A3, -C2, Tyrosinase, MelanA/MART-1, or gp100, and an HLA class II-targeting sequence. DCs were administered by 4-6 bi-weekly intradermal injections. IFN-α-2b (5 MIU TIW) was initiated either at recurrence (cohort 1), concomitant with DCs (cohorts 2 and 3), or following the fourth DC administration (cohort 4). RESULTS: Thirty melanoma patients were recruited between April 2006 and June 2009. DC-related adverse events included grade 2 local injection site reactions in all patients, grade 2 fever and flu-like symptoms in one patient, and skin depigmentation in seven patients. After a median follow-up of over 6 years, the median relapse-free survival is 22 months (95% CI 12-32 months). Twelve patients have died. The median overall survival has not been reached; the 2-year and 4-year survival rates are 93 and 70%, respectively. CONCLUSIONS: Adjuvant therapy following the resection of melanoma metastases with autologous mRNA-electroporated DCs, combined with interferon alfa-2b, is tolerable and results in encouraging long-term overall survival rates justifying further evaluation in a randomized clinical trial.

Among the most striking identity markers of a Buddhist monastic community are the robes worn by its members. It is therefore not surprising that disciplinary (vinaya) texts contain a wealth of guidelines on robes, and that much research has been done on how to make and wear such robes. The present article focuses on a much less studied, yet equally essential, aspect: the care of monastic robes. As we will see, disciplinary texts are similarly informative on this issue, although in this instance the guidelines are scattered throughout the various chapters of the vinayas. Taking care of one’s robes involved washing and dyeing them properly, and many details are provided on exactly how to do both. The vinayas offer a wealth of information on both the material culture of early Buddhist India and the monastic way to deal with the guidelines relating to robes. In sum, their rules provide an intriguing picture of how a Buddhist monastic community in India ideally took care of one of its most visible features — t...

// Kevin Van der Jeught 1 , Lukasz Bialkowski 1 , Lidia Daszkiewicz 1 , Katrijn Broos 1 , Cleo Goyvaerts 1 , Dries Renmans 1 , Sandra Van Lint 1 , Carlo Heirman 1 , Kris Thielemans 1 and Karine Breckpot 1 1 Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Laarbeeklaan, Jette, Belgium Correspondence: Karine Breckpot, email: // Keywords : Intratumoral, Immunotherapy, Tumor microenvironment, Immunomodulation, Vaccination Received : November 18, 2014 Accepted : December 24, 2014 Published : December 26, 2014 Abstract The identification of tumor-specific antigens and the immune responses directed against them has instigated the development of therapies to enhance antitumor immune responses. Most of these cancer immunotherapies are administered systemically rather than directly to tumors. Nonetheless, numerous studies have demonstrated that intratumoral therapy is an attractive approach, both for immunization and immunomodulation purposes. Injection, recruitment and/or activation of antigen-presenting cells in the tumor nest have been extensively studied as strategies to cross-prime immune responses. Moreover, delivery of stimulatory cytokines, blockade of inhibitory cytokines and immune checkpoint blockade have been explored to restore immunological fitness at the tumor site. These tumor-targeted therapies have the potential to induce systemic immunity without the toxicity that is often associated with systemic treatments. We review the most promising intratumoral immunotherapies, how these affect systemic antitumor immunity such that disseminated tumor cells are eliminated, and which approaches have been proven successful in animal models and patients.

The pharmaceutical and fine chemical industries are eager to strive toward innovative products and technologies. This study first derives hotspots in resource consumption of 2839 Basic Operations in 40 Active Pharmaceutical Ingredient synthesis steps through Exergetic Life Cycle Assessment (ELCA). Second, since companies are increasingly obliged to quantify the environmental sustainability of their products, two alternative ways of simplifying (E)LCA are discussed. The usage of averaged product group values (R(2) = 3.40 × 10(-30)) is compared with multiple linear regression models (R(2) = 8.66 × 10(-01)) in order to estimate resource consumption of synthesis steps. An optimal set of predictor variables is postulated to balance model complexity and embedded information with usability and capability of merging models with existing Enterprise Resource Planning (ERP) data systems. The amount of organic solvents used, molar efficiency, and duration of a synthesis step were shown to be the most significant predictor variables. Including additional predictor variables did not contribute to the predictive power and eventually weakens the model interpretation. Ideally, an organization should be able to derive its environmental impact from readily available ERP data, linking supply chains back to the cradle of resource extraction, excluding the need for an approximation with product group averages.