A monoclonal antibody-based immunoassay to measure the antibody response against the repeat region of the circumsporozoite protein of Plasmodium falciparum

Background: The malaria vaccine candidate RTS, S/AS01 (GSK Vaccines) induces high IgG concentration against the circumsporozoite protein (CSP) of Plasmodium falciparum. In human vaccine recipients circulating anti-CSP antibody concentrations are associated with protection against infection but appear not to be the correlate of protection. However, in a humanized mouse model of malaria infection prophylactic administration of a human monoclonal antibody (MAL1C), derived from a RTS, S/AS01-immunized volunteer, directed against the CSP repeat region, conveyed full protection in a dose-dependent manner suggesting that antibodies alone are able to prevent P. falciparum infection when present in sufficiently high concentrations. A competition ELISA was developed to measure the presence of MAL1C-like antibodies in polyclonal sera from RTS, S/AS01 vaccine recipients and study their possible contribution to protection against infection. Results: MAL1C-like antibodies present in polyclonal vaccine-induced sera were evaluated for their ability to compete with biotinylated monoclonal antibody MAL1C for binding sites on the capture antigen consisting of the recombinant protein encompassing 32 NANP repeats of CSP (R32LR). Serum samples were taken at different time points from participants in two RTS, S/AS01 vaccine studies (NCT01366534 and NCT01857869). Vaccine-induced protection status of the study participants was determined based on the outcome of experimental challenge with infected mosquito bites after vaccination. Optimal conditions were established to reliably detect MAL1C-like antibodies in polyclonal sera. Polyclonal anti-CSP antibodies and MAL1C-like antibody content were measured in 276 serum samples from RTS, S/AS01 vaccine recipients using the standard ELISA and MAL-1C competition ELISA, respectively. A strong correlation was observed between the results from these assays. However, no correlation was found between the results of either assay and protection against infection. Conclusions: The competition ELISA to measure MAL1C-like antibodies in polyclonal sera from RTS, S/AS01 vaccine recipients was robust and reliable but did not reveal the elusive correlate of protection

Unstable Identities: The European Court of Human Rights and the Margin of Appreciation

All legal systems work under a master narrative – the self-conception of most actors of the system itself. A master narrative is a short and simple story and it is the underlying premise upon which any legal system is based. It is a simple story because it paints the system in quick broad brushstrokes and at (most) times is oblivious to the paradoxes within it. Furthermore, a master narrative is important for legitimization purposes because the actors’ legitimacy will depend on their (perceived) conformity with the system’s master narrative. Therefore, legitimacy is self-referential; the yardsticks for a legitimate action are contained within the system’s master narrative, not outside of it. When talking about different international courts it is important to remember that they are embedded within a master narrative that is contextual and contingent and, at different points, more or less contested. This paper explores the question of what happens when the master-narrative is in a period of transition (from a state cantered to a post-national world order) and when the actors’ legitimacy, their interpretative endeavours the very fundamentals are in a state of flux. I use the margin of appreciation discussion as a focal point of describing the conflicting narratives under which the European Court of Human Rights works, narratives in which the different actors (judges, attorneys, NGO activists, government agents) and their consequences in terms of the interpretation of the European Convention on Human Rights

Importación y comercialización de insumos panificadores de la empresa comercial importadora Welfar E.I.R.L en Puente Piedra 2018

Comercial Importadora Welfar E.I.R.L es una empresa dedicado al rubro alimenticio en el Perú. Comercializa insumos para elaboración de panes, pasteles, tortas y helados. Su mayor mercado está en provincias del Perú. En la capital muy poco. En este sentido, el presente trabajo busca identificar los aspectos de la Importación en sus dos modalidades y las características de los aspectos que tiene la comercialización. El desarrollo de la presente investigación se basó en teorías que ayuda mucho para reforzar este estudio, tanto para la realización de Importación definitivas como las estrategias a emplear que serán parte de la empresa en su crecimiento. La investigación es de enfoque cualitativo, el diseño es interpretativa – teoría fundamentada y la técnica que se aplicó es la entrevista; con la finalidad de obtener datos informativos que responda a los problemas específicos y se origine soluciones. Finalmente, se conoció la problemática que se encontraba dentro de la empresa y se brindó objetivos para contrarrestar el mal y poder brindar una mejora para la empresa que a lo largo le servirá mucho para lo que quiere conseguir . Se consiguió respuestas en base a las entrevistas, que fueron hechas a una trabajadora de la empresa, al Director Gerente y a un experto en importaciones de la misma rama de la empresa

Exploring the influence of core-self evaluations, situational factors, and coping on nurse burnout : a cross-sectional survey study

Stress has become an inherent aspect of the nursing profession. Chronically experienced work stress can lead to burnout. Although situational stressors show a significant influence on burnout, their power to predict the complete syndrome is rather limited. After all, stressors only exist "in the eye of the beholder". This study aimed to explore how individual vulnerability factors such as core-self evaluations and coping, contribute to burnout in relation to situational stressors within a population of hospital nurses. Cross-sectional data was collected in 2014, using five validated self-report instruments: Dutch Core Self Evaluations Scale, Nursing Work Index Revised, Utrecht Coping List, Ruminative Response Scale, and Utrecht Burnout Scale. 219 of the 250 questionnaires were returned. Core-self evaluations, situational factors and coping each contributed significantly to the predictive capacity of the models of the separate burnout dimensions. Core-self evaluations was significantly related to emotional exhaustion. It was suggested that Core-self evaluations might be placed at the initiation of the loss cycle. However, further research is warranted

Grenseområdene Norge-Russland. Luft- og nedbørkvalitet, april 2014-mars 2015.

Smelteverkene på russisk side av den norsk-russiske grense slipper ut store mengder svoveldioksid (SO2) og tungmetaller. Dette gir forhøyede konsentrasjoner også på norsk side. Denne rapporten inngår i kartlegging av miljøbelastningen i grenseområdene og omfatter målinger av luftkvalitet, nedbørkvalitet og meteorologi

Validation of the AUDIT and AUDIT-C for hazardous drinking in community-dwelling older adults

Background: One of the best-known tools in screening for hazardous drinking is the Alcohol Use Disorders Identification Test (AUDIT) and its abbreviated form, the AUDIT-C. The aim of the present study is to determine the cut-offs of both instruments in identifying hazardous drinking in older adults. Method: A sample of 1577 older adults completed a questionnaire regarding alcohol behavior. Hazardous drinking was defined as drinking >10 units/week. Receiver operating characteristics (ROC) curves of AUDIT and AUDIT-C were calculated and cut-off scores were derived. Results: Respectively 27.3% and 12.3% of older men and women drank >10 units/week. For the AUDIT the best trade-off between sensitivity and specificity was using a cut-off of ≥5 for men and ≥4 for women, which yielded in men sensitivity and specificity values respectively of 80.7% and 81.3% and in women 100% and 71.7%, respectively. We found the AUDIT-C to perform well with an optimal cut-off of ≥5 for men and ≥4 for women, which generated in men sensitivity and specificity values respectively of 76.5% and 85.3% and in women 100% and 74.1%, respectively. Conclusion: The AUDIT-C is accurate and sufficient in screening for hazardous drinking in community-dwelling older adults if the cut-offs are tailored by gender

Radiative and mechanical feedback into the molecular gas in the Large Magellanic Cloud. I. N159W

We present Herschel SPIRE Fourier Transform Spectrometer (FTS) observations of N159W, an active star-forming region in the Large Magellanic Cloud (LMC). In our observations, a number of far-infrared cooling lines including CO(4-3) to CO(12-11), [CI] 609 and 370 micron, and [NII] 205 micron are clearly detected. With an aim of investigating the physical conditions and excitation processes of molecular gas, we first construct CO spectral line energy distributions (SLEDs) on 10 pc scales by combining the FTS CO transitions with ground-based low-J CO data and analyze the observed CO SLEDs using non-LTE radiative transfer models. We find that the CO-traced molecular gas in N159W is warm (kinetic temperature of 153-754 K) and moderately dense (H2 number density of (1.1-4.5)e3 cm-3). To assess the impact of the energetic processes in the interstellar medium on the physical conditions of the CO-emitting gas, we then compare the observed CO line intensities with the models of photodissociation regions (PDRs) and shocks. We first constrain the properties of PDRs by modelling Herschel observations of [OI] 145, [CII] 158, and [CI] 370 micron fine-structure lines and find that the constrained PDR components emit very weak CO emission. X-rays and cosmic-rays are also found to provide a negligible contribution to the CO emission, essentially ruling out ionizing sources (ultraviolet photons, X-rays, and cosmic-rays) as the dominant heating source for CO in N159W. On the other hand, mechanical heating by low-velocity C-type shocks with ~10 km/s appears sufficient enough to reproduce the observed warm CO.Comment: accepted for publication in A&

Efficient Training Set Use For Blood Pressure Prediction in a Large Scale Learning Classifier System

ABSTRACT We define a machine learning problem to forecast arterial blood pressure. Our goal is to solve this problem with a large scale learning classifier system. Because learning classifiers systems are extremely computationally intensive and this problem's eventually large training set will be very costly to execute, we address how to use less of the training set while not negatively impacting learning accuracy. Our approach is to allow competition among solutions which have not been evaluated on the entire training set. The best of these solutions are then evaluated on more of the training set while their offspring start off being evaluated on less of the training set. To keep selection fair, we divide competing solutions according to how many training examples they have been tested on

Effects of Electrode Configuration and Place of Stimulation on Speech Perception with Cochlear Prostheses

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42437/1/10162-2-2-87_10020087.pd

Design and characterization of extreme-ultraviolet broadband mirrors for attosecond science

International audienceA novel multilayer mirror was designed and fabricated based on a recently developed three-material technology aimed both at reaching reflectivities of about 20% and at controlling dispersion over a bandwidth covering photon energies between 35 and 50 eV. The spectral phase upon reflection was retrieved by measuring interferences in a two-color ionization process using high-order harmonics produced from a titanium: sapphire laser. We demonstrate the feasibility of designing and characterizing phase-controlled broadband optics in the extreme-ultraviolet domain, which should facilitate the manipulation of attosecond pulses for applications