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We performed a prospectively randomised clinical trial to compare the efficacy of four subcutaneous interleukin-2-(sc-IL-2) and sc interferon-alpha2a (sc-IFN-alpha2a)-based outpatient regimens in 379 patients with progressive metastatic renal cell carcinoma. Patients with lung metastases, an erythrocyte sedimentation rate < or =70 mm h(-1) and neutrophil counts < or =6000 microl(-1) (group I) were randomised to arm A: sc-IL-2, sc-IFN-alpha2a, peroral 13-cis-retinoic acid (po-13cRA) (n=78), or arm B: arm A plus inhaled-IL-2 (n=65). All others (group II) were randomised to arm C: arm A plus intravenous 5-fluorouracil (iv-5-FU) (n=116), or arm D: arm A plus po-Capecitabine (n=120). Median overall survival (OS) was 22 months (arm A; 3-year OS: 29.7%) and 18 months (arm B; 3-year OS: 29.2%) in group I, and 18 months (arm C; 3-year OS: 25.7%) and 16 months (arm D; 3-year OS: 32.6%) in group II. There were no statistically significant differences in OS, progression-free survival, and objective response between arms A and B, and between arms C and D, respectively. Given the known therapeutic efficacy of sc-IL-2/sc-INF-alpha2a/po-13cRA-based outpatient chemoimmunotherapies, our results did not establish survival advantages in favour of po-Capecitabine vs iv-5-FU, and in favour of short-term inhaled-IL-2 in patients with advanced renal cell carcinoma receiving systemic cytokines.

Background:A 2011 nationwide school pandemic preparedness study found schools to be deficient. We examined the impact of a school nurse educational intervention aimed at improving K-12 school biological event preparedness. Mehods: Missouri Association of School Nurses (MASN) members were e-mailed a survey link in fall 2013 (ie, preintervention), links to online education modules (ie, intervention) in late fall, and a postintervention survey link in spring, 2014. School biological event readiness was measured using 35 indicators, for a possible score range of 0-35. A paired t-test compared pre- to postintervention preparedness scores. Results: A total of 133 school nurses (33.6% response rate) completed a survey; 35.3% of those (N = 47) completed both pre- and postintervention survey that could be matched. Pre- and postintervention preparedness scores ranged from 5 to 28.5 (x-bar = 13.3) and 6.5 to 25 (x-bar = 14.8), respectively. Postintervention scores were significantly higher than preintervention scores for those who watched at least 1 module (t = -2.3, p < 0.05). Conclusion: The education intervention was effective at improving school preparedness, though the impact was small. The education intervention needs to be reassessed, especially in regard to providing a longer intervention period.

Introduction Little is known about childcare staff's and parents' uptake of and attitudes towards pertussis vaccine. Methods Questionnaires were distributed to St. Louis parents and childcare staff in fall, 2014. Parents versus staff and vaccinated versus unvaccinated individuals' beliefs regarding pertussis vaccine were compared using chi square tests. Multivariate logistic regressions were run to develop predictive models for staff's and parents' vaccine uptake. Results Overall, 351 parents and staff from 23 agencies participated (response rate = 32%). Parents were more likely than staff to have received pertussis vaccine (66.5 vs. 45.8%, X.sup.2 = 12.5, p < .001). Predictors for staff vaccination included willingness to get vaccinated even if there was a cost (OR 6.6; CI 1.8-24.6; p < .01), awareness of vaccination recommendations (OR 5.2; CI 1.2-22.8; p < .05), and healthcare provider recommendation (OR 4.2; CI 1.2-15.1; p < .05). Parents' predictors of vaccination included perceived importance of vaccination (OR 9.9; CI 4.1-23.8; p < .001), healthcare provider recommendation (OR 4.6; CI 1.7-12.6; p < .01), believing vaccination is effective (OR 4.4; CI 1.1-18.0; p < .05), and knowing where to get vaccine (OR 3.5; CI 1.5-8.1; p < .01). Among unvaccinated staff (n = 52), 74.5% (n = 38) and 70.0% (n = 35) would receive pertussis vaccine if it were offered free of charge and onsite, respectively. Conclusions for Practice Childcare staff's and parents' pertussis vaccine uptake was higher than overall U.S. rates, though significantly lower than the Global Pertussis Initiative target. Implementing an education campaign and providing free vaccine on-site are likely to result in increased vaccine uptake., Author(s): Terri Rebmann [sup.1] [sup.3] , Travis M. Loux [sup.2] , Daphne Lew [sup.2] , Mary Wakefield [sup.1] Author Affiliations: (1) Institute for Biosecurity, Epidemiology & Biostatistics, College for Public [...]

In the last few years the method of cosmic-ray neutron sensing (CRNS) has gained popularity among hydrologists, physicists, and land-surface modelers. The sensor provides continuous soil moisture data, averaged over several hectares and tens of decimeters in depth. However, the signal still may contain unidentified features of hydrological processes, and many calibration datasets are often required in order to find reliable relations between neutron intensity and water dynamics. Recent insights into environmental neutrons accurately described the spatial sensitivity of the sensor and thus allowed one to quantify the contribution of individual sample locations to the CRNS signal. Consequently, data points of calibration and validation datasets are suggested to be averaged using a more physically based weighting approach. In this work, a revised sensitivity function is used to calculate weighted averages of point data. The function is different from the simple exponential convention by the extraordinary sensitivity to the first few meters around the probe, and by dependencies on air pressure, air humidity, soil moisture, and vegetation. The approach is extensively tested at six distinct monitoring sites: two sites with multiple calibration datasets and four sites with continuous time series datasets. In all cases, the revised averaging method improved the performance of the CRNS products. The revised approach further helped to reveal hidden hydrological processes which otherwise remained unexplained in the data or were lost in the process of overcalibration. The presented weighting approach increases the overall accuracy of CRNS products and will have an impact on all their applications in agriculture, hydrology, and modeling.

Background: Harvest of oral mucosa for urethroplasty due to urethral stricture is associated with donor-site-morbidity. We assessed functionality and safety of an authorized tissue-engineered oral mucosa graft (TEOMG) under routine practice in stricture recurrences of any etiology, location, length and severity (real-world data). Methods: 99 patients from eight centers with heterogenous urethroplasty experience levels were included in this prospective, non-interventional observational study. Primary and secondary outcomes were success rate (SR) and safety at 12 and 24 months. Findings: All but one patient had ≥1, 77.1% (64 of 83) ≥ 2 and 31.3% (26 of 83) ≥ 4 previous surgical treatments. Pre- and postoperative mean ± SD peak flow rate (Qmax) were 8.3 ± 4.7 mL/s (n = 57) and 25.4 ± 14.7 mL/s (n = 51). SR was 67.3% (95% CI 57.6–77.0) at 12 and 58.2% (95% CI 47.7–68.7) at 24 months (conservative Kaplan Meier assessment). SR ranged between 85.7% and 0% in case of high and low surgical experience. Simple proportions of 12-month and 24-month SR for evaluable patients in all centers were 70.8% (46 of 65) and 76.9% (30 of 39). Except for one patient, no oral adverse event was reported. Interpretations: TEOMG is safe and efficient in urethroplasty.

This article charts the development of activities for online graduate students in library and information science. Project goals include helping students develop competencies in understanding open access publishing, synthesizing research in the field, and engaging in scholarly communication via collaborative educational blogging. Using a design experiment approach as a research strategy, focus is placed on the design of the collaborative blogging activity, open access research as a knowledge domain, and analyses of four iterations of the project. Findings from this iterative learning design suggest several benefits of implementing collaborative educational blogging activities in distance contexts.

Abstract An appropriate antibiotherapy is crucial for the safety and recovery of patients. Depending on the clinical conditions of patients, the required dose to effectively eradicate an infection may vary. An inadequate dosing not only reduces the efficacy of the antibiotic, but also promotes the emergence of antimicrobial resistances. Therefore, a personalized therapy is of great interest for improved patients’ outcome and will reduce in long-term the prevalence of multidrug-resistances. In this context, on-site monitoring of the antibiotic blood concentration is fundamental to facilitate an individual adjustment of the antibiotherapy. Herein, we present a bioinspired approach for the bedside monitoring of free accessible ß-lactam antibiotics, including penicillins (piperacillin) and cephalosporins (cefuroxime and cefazolin) in untreated plasma samples. The introduced system combines a disposable microfluidic chip with a naturally occurring penicillin-binding protein, resulting in a high-performance platform, capable of gauging very low antibiotic concentrations (less than 6 ng ml−1) from only 1 µl of serum. The system’s applicability to a personalized antibiotherapy was successfully demonstrated by monitoring the pharmacokinetics of patients, treated with ß-lactam antibiotics, undergoing surgery.

Abstract Background Capturing the response of forest ecosystems to inter-annual climate variability is a great challenge. In this study, we tested the capability of an individual-based forest gap model to display carbon fluxes at yearly and daily time scales. The forest model was applied to a spruce forest to simulate the gross primary production (GPP), respiration and net ecosystem exchange (NEE). We analyzed how the variability in climate affected simulated carbon fluxes at the scale of the forest model. Results Six years were simulated at a daily time scale and compared to the observed eddy covariance (EC) data. In general, the seasonal cycle of the individual carbon fluxes was correctly described by the forest model. However, the estimated GPP differed from the observed data on the days of extreme climatic conditions. Two new parameterizations were developed: one resulting from a numerical calibration, and the other resulting from a filtering method. We suggest new parameter values and even a new function for the temperature limitation of photosynthesis. Conclusions The forest model reproduced the observed carbon fluxes of a forest ecosystem quite well. Of the three parameterizations, the calibrated model version performed best. However, the filtering approach showed that calibrated parameter values do not necessarily correctly display the individual functional relations. The concept of simulating forest dynamics at the individual base is a valuable tool for simulating the NEE, GPP and respiration of forest ecosystems.

Im Rahmen der UN-Behindertenrechtskonvention (BRK) hat sich Deutschland verpflichtet, Maßnahmen zur Förderung des Bewusstseins für die Belange von Menschen mit Behinderung zu ergreifen. Dies schließt die Verpflichtung ein, auf eine mediale Darstellung dieser Menschen hinzuwirken, die dem Zweck der BRK entspricht. Der Beitrag diskutiert, was eine zweckkonforme Darstellung ausmacht, und stellt ein inhaltsanalytisches Messinstrument vor, mit dem zwei zentrale Merkmale der Darstellung von Menschen mit Behinderung erfasst werden können: (1) Die Präsenz von Menschen mit Behinderung und (2) die Problematisierung von Themen, auf die sich die Ansprüche der BRK beziehen (z. B. Barrierefreiheit). Das Messinstrument wurde in zwei Inhaltsanalysen populärer deutscher Daily Soaps erprobt. Die Befunde zeigen, dass Menschen mit Behinderung in Serien öffentlich-rechtlicher Fernsehsender präsenter sind als in Serien des Privatfernsehens, und dass ihre Vielfalt in Daily Soaps nicht adäquat repräsentiert ist. Die Themen der BRK werden umfassend und im Serienangebot der öffentlich-rechtlichen Sender auch kontinuierlich problematisiert. Der Beitrag diskutiert, welche Rolle solche empirischen Analysen in einem umfassenderen Engagement kommunikationswissenschaftlicher Forschung im Inklusionsprozess spielen können.

TV Whitespace (TVWS) represents one new wireless communication technology that has the potential to improve internet access and inclusion. This primer describes TVWS technology as a viable, long-term access solution for the benefit of public libraries and their communities, especially for underserved populations. Discussion focuses first on providing a brief overview of the digital divide and the emerging role of public libraries as internet access providers. Next, a basic description of TVWS and its features is provided, focusing on key aspects of the technology relevant to libraries as community anchor institutions. Several TVWS implementations are described with discussion of TVWS implementations in several public libraries. Finally, consideration is given to first steps that library organizations must take when contemplating new TVWS implementations supportive of Wi-Fi applications and crisis response planning.

Introduction: Response to platinum-based therapy is a major prognostic factor in epithelial ovarian cancer (EOC) and reliable prognostic biomarkers are urgently needed to identify patients at high risk. Since ligands of the Programmed Death Receptor-1 (PD-L1 and PD-L2) play a crucial role within the tumor microenvironment for tumorigenesis, we investigated levels of sPD-L1 and sPD-L2 in liquid biopsies of serum samples, and correlated the results with the clinical status, presence of circulating tumor cells (CTCs) and disease outcome in primary EOC patients.Methods: sPD-L1 and sPD-L2 were determined by ELISA in patients (N = 83) and healthy females (N = 29). Gene expression analysis of EpCAM, MUC-1, CA-125, and ERCC1 was performed by RT-PCR after CTCs enrichment.Results: sPD-L1 was significantly (p = 0.0001) increased and sPD-L2 decreased (p = 0.003) in EOC patients compared to controls. While enhanced sPD-L1 was associated with residual tumor burden (p = 0.022), reduced sPD-L2 levels were related to platinum-resistance (p < 0.01) and the presence of ERCC1+ CTCs (p < 0.0001). High sPD-L1 levels were associated with a reduced 5 year overall survival (OS, p = 0.003) and progression-free survival (PFS, p = 0.019). Strikingly, sPD-L1 levels >6.4 pg/ml were indicative of a reduced OS (p = 0.035) and PFS (p = 0.083) in platinum-sensitive patients, while OS and PFS in platinum-resistant patients did not differ when patients were stratified to this cut-off.Conclusions: Our study highlights sPD-L1 and sPD-L2 as complementary biomarkers reflecting clinical status, treatment response and disease outcome of EOC patients. Especially, sPD-L1 may facilitate the identification of high-risk patients with unfavorable disease outcomes despite platinum-sensitivity arguing for additional therapeutic approaches. As sPD-L1 and sPD-L2 are easily accessible via liquid biopsy, the inclusion of sPD-L1 and sPD-L2 in addition to CTC investigation as markers for risk assessment during patient therapy planning and follow-up appears to be a valuable approach.

Molecular tweezers (MTs) are supramolecular host molecules equipped with two aromatic pincers linked together by a spacer (Gakh, 2018). They are endowed with fascinating properties originating from their ability to hold guests between their aromatic pincers (Chen and Whitlock, 1978; Zimmerman, 1991; Harmata, 2004). MTs are finding an increasing number of medicinal applications, e.g., as bis-intercalators for DNA such as the anticancer drug Ditercalinium (Gao et al., 1991), drug activity reverters such as the bisglycoluril tweezers Calabadion 1 (Ma et al., 2012) as well as radioimmuno detectors such as Venus flytrap clusters (Paxton et al., 1991). We recently embarked on a program to create water-soluble tweezers which selectively bind the side chains of lysine and arginine inside their cavity. This unique recognition mode is enabled by a torus-shaped, polycyclic framework, which is equipped with two hydrophilic phosphate groups. Cationic amino acid residues are bound by the synergistic effect of disperse, hydrophobic, and electrostatic interactions in a kinetically fast reversible process. Interactions of the same kind play a key role in numerous protein-protein interactions, as well as in pathologic protein aggregation. Therefore, these particular MTs show a high potential to disrupt such events, and indeed inhibit misfolding and self-assembly of amyloidogenic polypeptides without toxic side effects. The mini-review provides insight into the unique binding mode of MTs both toward peptides and aggregating proteins. It presents the synthesis of the lead compound CLR01 and its control, CLR03. Different biophysical experiments are explained which elucidate and help to better understand their mechanism of action. Specifically, we show how toxic aggregates of oligomeric and fibrillar protein species are dissolved and redirected to form amorphous, benign assemblies. Importantly, these new chemical tools are shown to be essentially non-toxic in vivo. Due to their reversible moderately tight binding, these agents are not protein-, but rather process-specific, which suggests a broad range of applications in protein misfolding events. Thus, MTs are highly promising candidates for disease-modifying therapy in early stages of neurodegenerative diseases. This is an outstanding example in the evolution of supramolecular concepts toward biological application.