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Ever since the 1996 revision of the Declaration of Helsinki, the World Medical Association has attempted to address ethical and scientific concerns of its diverse stakeholders for Articles 33 (use of placebo) and 34 (posttrial provisions), most recently in 2013. Both are inextricably linked to standard of care, an essential element of any comparative, interventional clinical trial. But has this now 20-year-long ethical debate truly been put to rest? The choice of standard of care in clinical trials remains a complex issue, particularly for comparative trials conducted in emerging countries.
Context: Agile software development (ASD) sets social aspects like communication and collaboration in focus. Thus, one may assume that the specific work organization of companies impacts the work of ASD teams. A major change in work organization is the switch to a 4-day work week, which some companies investigated in experiments. Also, recent studies show that ASD teams are affected by the switch to remote work since the Covid 19 pandemic outbreak in 2020.
Objective: Our study presents empirical findings on the effects on ASD teams operating remote in a 4-day work week organization. Method: We performed a qualitative single case study and conducted seven semi-structured interviews, observed 14 agile practices and screened eight project documents and protocols of agile practices.
Results: We found, that the teams adapted the agile method in use due to the change to a 4-day work week environment and the switch to remote work. The productivity of the two ASD teams did not decrease. Although the stress level of the ASD team member increased due to the 4-day work week, we found that the job satisfaction of the individual ASD team members is affected positively. Finally, we point to affects on social facets of the ASD teams.
Conclusion: The research community benefits from our results as the current state of research dealing with the effects of a 4-day work week on ASD teams is limited. Also, our findings provide several practical implications for ASD teams working remote in a 4-day work week.
Flatness-based feedforward control is an approach for combining fast motion with low oscillations for nonlinear or flexible drive systems. Its desired trajectories must be continuously differentiable to the degree of the system order. Designing such trajectories, that also reach the dynamic system limits, poses a challenge. Common solutions, like Gevrey functions, usually require lengthy offline calculations. To achieve a quicker and simpler industrial-suited solution, this paper presents a new online trajectory generation scheme. The algorithm utilizes higher order s-curve trajectories created by a cyclic filtering process using moving average filters. An experimental validation proves the capability as well as industrial applicability of the presented approach for flexible structures like stacker cranes.
The lytic efficacy of bacteriophages against Staphylococcus aureus isolates from bovine milk was investigated in vitro, regarding possible applications in the therapy of udder inflammation caused by bacterial infections (mastitis). The host range of sequenced, lytic bacteriophages was determined against a collection of 92 Staphylococcus (S.) aureus isolates. The isolates originated from quarter foremilk samples of clinical and subclinical mastitis cases. A spot test and a subsequent plaque assay were used to determine the phage host range. According to their host range, propagation and storage properties, three phages, STA1.ST29, EB1.ST11, and EB1.ST27, were selected for preparing a bacteriophage mixture (1:1:1), which was examined for its lytic activity against S. aureus in pasteurized and raw milk. It was found that almost two thirds of the isolates could be lysed by at least one of the tested phages. The bacteriophage mixture was able to reduce the S. aureus germ density in pasteurized milk and its reduction ability was maintained in raw milk, with only a moderate decrease compared to the results in pasteurized milk. The significant reduction ability of the phage mixture in raw milk promotes further in vivo investigation.
The antimicrobial activity of a phagemixture and a lactic acid bacteriumagainst Staphylococcus aureus isolates from bovine origin was investigated in vitro with regard to possible applications in the therapy of udder inflammation (mastitis) caused by bacterial infections. The S. aureus isolates used for inoculation derived from quarter foremilk samples of mastitis cases. For the examination of the antimicrobial activity, the reduction of the S. aureus germ density was determined [log10 cfu/mL]. The phage mixture consisted of the three obligatory lytic and S. aureus-specific phages STA1.ST29, EB1.ST11 and EB1.ST27 (1:1:1). The selected Lactobacillus plantarum strain with proven antimicrobial properties and the phage mixture were tested against S. aureus in milk, both alone and in combination. The application of the lactic acid bacterium showed only a low reduction ability for a 24 h incubation period. The bacteriophage mixture as well as its combination with the lactic acid bacterium showed high antimicrobial activity against S. aureus for a 24 h incubation period at 37 C, with only the phage mixture showing significance.
A study to assess the knowledge and attitude towards HIV of pharmacy students from Mumbai university
(2020)
Background: India is the biggest HIV epidemic in the world. The role of a pharmacist is pivotal in educating the general masses. The aim of the study was to determine the knowledge and attitude of pharmacy students from University of Mumbai.
Methods: A cross-sectional study was conducted in University of Mumbai during February-March 2020. Therein, 307 students (214: females and 94: males) participated in the study. The questionnaire was distributed in the classroom and data was collected by means of Google-forms. Furthermore, the data was analysed using IBM SPSS version 23.
Results: The participants demonstrated good knowledge (84%) and attitude (76%) score. With respect to knowledge score, no significant difference was observed except for responses of two questions, aim of the antiretroviral therapy (ART) and Avoidance of sexual intercourse can decrease the risk of HIV. With respect to attitude score, Volunteering to work at an institute for the welfare of HIV patients showed a significant difference.
Conclusion: The current study showed that there were no misconceptions or negative attitude regarding HIV among the students. However, a study with greater sample size must be conducted across India for further investigation.
Industrial Control Systems (ICS) succumb to an ever evolving variety of threats. Additionally, threats are increasing in number and get more complex. This requires a holistic and up-to-date security concept for ICS as a whole. Usually security concepts are applied and updated based on regularly performed ICS security assessments. Such ICS security assessments require high effort and extensive knowledge about ICS and its security. This is often a problem for small and mediumsized enterprises (SME), which do not have sufficient respective sufficiently skilled human resources. This paper defines in a first step requirements on the knowledge needed to perform an ICS security assessment and the life cycle of this knowledge. Afterwards the ICS security knowledge and its life cycle are developed and discussed considering the requirements and related work.
Catholic Ownership, Physician Leadership and Operational Strategies: Evidence from German Hospitals
(2022)
Previous research has revealed that Catholic hospitals are more likely follow a strategy of horizontal diversification and maximization of the number of patients treated, whereas Protestant hospitals follow a strategy of horizontal specialization and focus on vertical differentiation. However, there is no empirical evidence pertaining to this mechanism. We conduct an empirical study in a German setting and argue that physician leadership mediates the relationship between ownership and operational strategies. The study includes the construction of a model combining data from a survey and publicly available information derived from the annual quality reports of German hospitals. Our results show that Catholic hospitals opt for leadership structures that ensure operational strategies in line with their general values, i.e., operational strategies of maximizing volume throughout the overall hospital. They prefer part-time positions for chief medical officers, as chief medical officers are identified to foster strategies of maximizing the overall number of patients treated. Hospital owners should be aware that the implementation of part-time and full-time leadership roles can help to support their strategies. Thus, our results provide insights into the relationship between leadership structures at the top of an organization, on the one hand, and strategic choices, on the other.
In the last years generative models have gained large public attention due to their high level of quality in generated images. In short, generative models learn a distribution from a finite number of samples and are able then to generate infinite other samples. This can be applied to image data. In the past generative models have not been able to generate realistic images, but nowadays the results are almost indistinguishable from real images.
This work provides a comparative study of three generative models: Variational Autoencoder (VAE), Generative Adversarial Network (GAN) and Diffusion Models (DM). The goal is not to provide a definitive ranking indicating which one of them is the best, but to qualitatively and where possible quantitively decide which model is good with respect to a given criterion. Such criteria include realism, generalization and diversity, sampling, training difficulty, parameter efficiency, interpolating and inpainting capabilities, semantic editing as well as implementation difficulty. After a brief introduction of how each model works on the inside, they are compared against each other. The provided images help to see the differences among the models with respect to each criterion.
To give a short outlook on the results of the comparison of the three models, DMs generate most realistic images. They seem to generalize best and have a high variation among the generated images. However, they are based on an iterative process, which makes them the slowest of the three models in terms of sample generation time. On the other hand, GANs and VAEs generate their samples using one single forward-pass. The images generated by GANs are comparable to the DM and the images from VAEs are blurry, which makes them less desirable in comparison to GANs or DMs. However, both the VAE and the GAN, stand out from the DMs with respect to the interpolations and semantic editing, as they have a latent space, which makes space-walks possible and the changes are not as chaotic as in the case of DMs. Furthermore, concept-vectors can be found, which transform a given image along a given feature while leaving other features and structures mostly unchanged, which is difficult to archive with DMs.
The objective of this study was to investigate the association between teat skin colonization and intramammary infection (IMI) with Staphylococcus aureus or Streptococcus agalactiae at the quarter level in herds with automatic milking systems. Milk and teat skin samples from 1,142 quarters were collected from 300 cows with somatic cell count >200,000 cells/mL from 8 herds positive for Strep. agalactiae. All milk and teat skin samples were cultured on calf blood agar and selective media. A subset of samples from 287 quarters was further analyzed using a PCR assay (Mastit4 PCR; DNA Diagnostic A/S, Risskov, Denmark). Bacterial culture detected Staph. aureus in 93 (8.1%) of the milk samples and 75 (6.6%) of the teat skin samples. Of these, 15 (1.3%) quarters were positive in both the teat skin and milk samples. Streptococcus agalactiae was cultured in 84 (7.4%) of the milk samples and 4 (0.35%) of the teat skin samples. Of these, 3 (0.26%) quarters were positive in both the teat skin and milk samples. The PCR detected Staph. aureus in 29 (10%) of the milk samples and 45 (16%) of the teat skin samples. Of these, 2 (0.7%) quarters were positive in both the teat skin and milk samples. Streptococcus agalactiae was detected in 40 (14%) of the milk samples and 51 (18%) of the teat skin samples. Of these, 16 (5.6%) quarters were positive in both the teat skin and milk samples. Logistic regression was used to investigate the association between teat skin colonization and IMI at the quarter level. Based on bacterial culture results, teat skin colonization with Staph. aureus resulted in 7.8 (95% confidence interval: 2.9; 20.6) times higher odds of Staph. aureus IMI, whereas herd was observed as a major confounder. However, results from the PCR analyses did not support this association. Streptococcus agalactiae was isolated from the teat skin with both PCR and bacterial culture, but the number of positive teat skin samples detected by culture was too low to proceed with further analysis. Based on the PCR results, Strep. agalactiae on teat skin resulted in 3.8 (1.4; 10.1) times higher odds of Strep. agalactiae IMI. Our results suggest that Staph. aureus and Strep. agalactiae on teat skin may be a risk factor for IMI with the same pathogens. Focus on proper teat skin hygiene is therefore recommended also in AMS.
This paper presents a cascaded methodology for enhancing the path accuracy of industrial robots by using advanced control schemes. It includes kinematic calibration as well as dynamic modeling and identification. This is followed by a centralized model-based compensation of robot dynamics. The implemented feed-forward torque control shows the expected improvements of control accuracy. However, external measurements show the influence of joint elasticities as systematic path errors. To further increase the accuracy an iterative learning controller (ILC) based on external camera measurements is designed. The implementation yields to significant improvements of path accuracy. By means of a kind of automated ”Teach-In”, an overall effective concept for the automated calibration and optimization of the accuracy of industrial robots in high-dynamic path-applications is realized.
Background
The business of clinical research has changed in the past two decades, shifting from industrialised Western countries to so-called emerging markets such as Eastern Europe, Latin America and Africa. An appraisal of the trends could identify associated factors that may have implications for the local populations and their endemic diseases.
Objectives
To identify potential reasons why emerging countries have become attractive places for international sponsors to conduct their clinical trials.
Methods
Using ClinicalTrials.gov, the Pan African Clinical Trials Registry, the National Health Research Database and the Nigeria Clinical Trials Registry, trend data on clinical research development were determined for two emerging African markets, Nigeria and South Africa (SA), from 2010 to 2018. Also, health data on the two countries from the fact sheets of health statistics of the World Health Organization were compared, as well as regulatory and ethical conditions. Available data were analysed using descriptive statistics and trend analysis.
Results
The impact of globalisation is evident from the upward trend in clinical trials in SA before 2010, and the clear downward trend thereafter. One reason for this change could be the alignment of SA’s regulatory and ethical frameworks with the Western world. In contrast,
the upward trend is only just beginning in Nigeria, with the introduction of ethical/regulatory frameworks, and supportive institutions making the business of clinical research more attractive on an international level. Although the number of international and local sponsors increased in Nigeria from 2010 to 2018, only the latter increased in SA, with the former decreasing over the same period. Overall, there is a mismatch between country-specific diseases and the drugs being tested, to the extent that leprosy, which is endemic in Nigeria, and tuberculosis in SA were not in the list of top 10 study areas in either country.
Conclusions
The globalisation trend is evident in the clinical trials business, but cannot be generalised to all emerging countries. Timing and intensity vary from country to country relative to factors that advance the existing profit-orientated business models of the sponsors. Furthermore, various diseases have been localised, which entails a diversely increasing need for research.
Economic and political/governmental infrastructural factors are major contributors to the economic development/growth of all sectors of a country, such as in the area of healthcare systems and clinical research, including the pharmaceutical industry. But what is the interaction between economic, and political/governmental infrastructural factors and the development of healthcare systems, especially, the performance of the pharmaceutical industry? Information from selected articles of a literature search of PubMed and by using Google Advanced Search led to the generation of five categories of infrastructural factors, and were filled with data from 41 African Countries using the World Health Organization data repository. Median changes over time were given and tested by Wilcoxon signed-rank test and Friedman test, respectively. Analysis of factors related to availability of healthcare facilities showed that physicians and pharmacies were significant increased, with insignificantly decreased number of hospital beds. Healthcare Financing by the Government showed notable differences. Private health spending decreased significantly unlike Gross National Income. Analysis of infrastructural factors showed that stable supply of electricity and the associated use of the Internet improved significantly. The low level of data on the expansion of paved road networks suggests less developed medical services in remote rural areas. Healthcare systems in African countries improved over the last two decades, but differences between the individual countries still prevail and some of the countries cannot yet offer an attractive sales market for the products of pharmaceutical companies.
Background: The globalization of clinical research should also benefit the population in developing markets. In this context, the approval of tested medicines and the associated expansion of medical care beyond clinical studies would be desirable as a possible long-term benefit.
Objectives: This study was designed to compare the development of the number of clinical trials with the number of marketing authorizations of medicines on the African continent. To contrast these 2 parameters, the data were analyzed using the model of an ecological study.
Methods: To reflect the broad spectrum of African developing countries with diverse levels of development, the data collection was based on 2 geographically selected sample countries each from Central, North, East, West, and Southern Africa. Based on the ClinicalTrials.gov registry, the first step was to collect trends data on the development of the clinical trials in the 10 selected countries of the country list of the African Region published by the World Health Organization for the period 2015 to 2018. Subsequently, data on the current number of marketing authorizations of medicines in the selected sample countries were identified using the online registries of the national authorities. The data were utilized in comparative analyses.
Results: Eight out of 10 model countries showed an increase in the number of clinical trials, with the exceptions of Cameroon and Libya, which showed an overall decline in research activity over the entire time. In direct comparison with drug registrations, the numbers indicate a similar development. The only exception here is Nigeria, a country with a solid performance in clinical research and yet a decrease in medicine registrations since 2015.
Conclusions: The expected increase in the development of clinical research as result of the globalization trend can basically be observed in most of the model countries. However, this increase does not guarantee an improvement in the number of medicine registrations. Although this is evident in some of the selected model countries, it cannot be projected to the entire African region. This may be linked to the diverse development of the individual countries due to the different political situations and the varying degrees of clinical research infrastructure.
Objectives:
The aim was to identify theoretically expected as well as actually reported benefits from drug development and the importance of individual patient benefits compared to the collective benefits to society in general.
Background:
Ethical guidelines require that clinical research involving humans offer the potential for benefit. A number of characteristics can be applied to define research benefit. Often benefit is categorized as being either direct or indirect. Indirect benefits can involve collective benefits for society rather than any benefits to the trial patient or subject. The purpose of this review was to examine which potential individual and societal benefits were mentioned as being expected in publications from government experts and which were mentioned in publications describing completed drug development trial results.
Methods:
Literature on research benefit was first identified by searching the PubMed database using several combinations of the key words benefit and clinical research. The search was limited to articles published in English. A Google search with the same combinations of key words but without any language limitation was then performed. Additionally, the reference lists of promising articles were screened for further thematically related articles. Finally, a narrative review was performed of relevant English- and German-language articles published between 1996 and 2016 to identify which of several potential benefits were either theoretically expected or which were mentioned in publications on clinical drug development trial results.
Results:
The principal benefits from drug development discussed included 2 main types of benefit, namely individual benefits for the patients and collective benefits for society. Twenty-one of an overall total of 26 articles discussing theoretically expected benefits focused on individual patient benefits, whereas 17 out of 26 articles mentioned collective benefits to society. In these publications, the most commonly mentioned theoretically expected individual patient benefit was the chance to receive up-to-date care (38.1%). A general increase in knowledge about health care, treatments, or drugs (70.6%) was the most commonly mentioned theoretically expected benefit for society. In contrast, all 13 publications reporting actual benefits of clinical drug development trials focused on personal benefits and only 1 of these publications also mentioned a societal benefit. The most commonly mentioned individual benefit was an increased quality of life (53.9%), whereas the only mentioned collective benefit to society was a general gain of knowledge (100.0%).
Conclusions:
Both theoretically expected and actually reported benefits in the majority of the included publications emphasized the importance of individual patient benefits from drug development rather than the collective benefits to society in general. The authors of these publications emphasized the right of each individual patient or subject to look for and expect some personal benefit from participating in a clinical trial rather than considering societal benefit as a top priority. From an ethical point of view, the benefits each individual patient receives from his or her participation in a clinical trial might also be seen as a societal benefit, especially when the drug or device tested, if approved for marketing, would eventually be made available for other similar patients from the country in which the clinical trial was conducted.
From an ethical perspective, clinical research involving humans is only acceptable if it involves the potential for benefit. Various characteristics can be applied to differentiate research benefit. Often benefit is categorized in direct or indirect benefit, whereby indirect benefit might be further differentiated in collective or benefit for the society, excluding or including the trial patient in the long term. Ethical guidelines, such as the Declaration of Helsinki in its latest version, do not precisely favor a particular type of benefit.
Publication Bias
(2016)
According to the Declaration of Helsinki, as well as the Statement on Public Disclosure of Clinical Trial Results of the World Health Organization, every researcher has the ethical obligation to publish research results on all trials with human participants in a complete and accurate way within 12 months after the end of the trial.1,2 Nevertheless, for several reasons, not all research results are published in an accurate way in case they are released at all. This phenomenon of publication bias may not only create a false impression on the reliability of clinical research business, but it may also affect the evidence of clinical conclusions about the best treatments, which are mostly based on published data and results.
Delphi is a frequently used research method in the information systems (IS) field. The last fifteen years have seen many variants of the Delphi Method proposed and used in IS research. However, these variants do not seem to be properly derived; while all variants share certain characteristics, their reasoning for differentiation inconsistently varies. It seems that researchers tend to create “new” Delphi Method variants, although the underlying modification of the Delphi Method is, in fact, minor. This leads to a heterogeneity of Delphi Method variants and undermines scientific rigor when using Delphi. The study addresses this deficit and (1) identifies different variants of Delphi and determines their characteristics, (2) critically reflects to what extent a clear distinction between these variants exists, (3) shows the clearly distinguishable Delphi Method variants and their characteristics, (4) develops a proposed taxonomy of Delphi Method variants, and (5) evaluates and applies this taxonomy. The proposed taxonomy helps clearly differentiate Delphi Method variants and enhances methodological rigor when using the Delphi Method.
The growing importance of renewable generation connected to distribution grids requires an increased coordination between transmission system operators (TSOs) and distribution system operators (DSOs) for reactive power management. This work proposes a practical and effective interaction method based on sequential optimizations to evaluate the reactive flexibility potential of distribution networks and to dispatch them along with traditional synchronous generators, keeping to a minimum the information exchange. A modular optimal power flow (OPF) tool featuring multi-objective optimization is developed for this purpose. The proposed method is evaluated for a model of a real German 110 kV grid with 1.6 GW of installed wind power capacity and a reduced order model of the surrounding transmission system. Simulations show the benefit of involving wind farms in reactive power support reducing losses both at distribution and transmission level. Different types of setpoints are investigated, showing the feasibility for the DSO to fulfill also individual voltage and reactive power targets over multiple connection points. Finally, some suggestions are presented to achieve a fair coordination, combining both TSO and DSO requirements.
Background: To improve interprofessional collaboration between registered nurses (RNs) and general practitioners (GPs) for nursing home residents (NHRs), the interprof ACT intervention package was developed. This complex intervention includes six components (e.g., shared goal setting, standardized procedures for GPs’ nursing home visits) that can be locally adapted. The cluster‑randomized interprof ACT trial evaluates the effects of this intervention on the cumulative incidence of hospital admissions (primary outcome) and secondary outcomes (e.g., length of hospital stays, utilization of emergency care services, and quality of life) within 12 months. It also includes a process evaluation which is subject of this protocol. The objectives of this evaluation are to assess the implementation of the interprof ACT intervention package and downstream effects on nurse–physician collaboration as well as preconditions and prospects for successive implementation into routine care.
Methods: This study uses a mixed methods triangulation design involving all 34 participating nursing homes (clusters). The quantitative part comprises paper‑based surveys among RNs, GPs, NHRs, and nursing home directors at baseline and 12 months. In the intervention group (17 clusters), data on the implementation of preplanned implementation strategies (training and supervision of nominated IPAVs, interprofessional kick‑off meetings) and local implementation activities will be recorded. Major outcome domains are the dose, reach and fidelity of the implementation of the intervention package, changes in interprofessional collaboration, and contextual factors. The qualitative part will be conducted in a subsample of 8 nursing homes (4 per study group) and includes repeated non‑participating observations and semistructured interviews on the interaction between involved health professionals and their work processes. Quantitative and qualitative data will be descriptively analyzed and then triangulated by means of joint displays and mixed methods informed regression models.
Discussion: By integrating a variety of qualitative and quantitative data sources, this process evaluation will allow comprehensive assessment of the implementation of the interprof ACT intervention package, the changes induced in interprofessional collaboration, and the influence of contextual factors. These data will reveal expected and unexpected changes in the procedures of interprofessional care delivery and thus facilitate accurate conclusions for the further design of routine care services for NHRs.
The research project "Herbar Digital" was started in 2007 with the aim to digitize 3.5 million dried plants on paper sheets belonging to the Botanic Museum Berlin in Germany. Frequently the collector of the plant is unknown, so a procedure had to be developed in order to determine the writer of the handwriting on the sheet. In the present work the static character was transformed into a dynamic form. This was done with the model of an inert ball which was rolled along the written character. During this off-line writer recognition, different mathematical procedures were used such as the reproduction of the write line of individual characters by Legendre polynomials. When only one character was used, a recognition rate of about 40% was obtained. By combining multiple characters, the recognition rate rose considerably and reached 98.7% with 13 characters and 93 writers (chosen randomly from the international IAM-database [3]). A global statistical approach using the whole handwritten text resulted in a similar recognition rate. By combining local and global methods, a recognition rate of 99.5% was achieved.
Our research project, "Rationalizing the virtualization of botanical document material and their usage by process optimization and automation (Herbar-Digital)" started on July 1, 2007 and will last until 2012. Its long-term aim is the digitization of the more than 3,5 million specimens in the Berlin Herbarium. The University of Applied Sciences and Arts in Hannover collaborates with the department of Biodiversity Informatics at the BGBM (Botanic Garden and Botanical Museum Berlin-Dahlem) headed by Walter Berendsohn. The part of Herbar-Digital here presented deals with the analysis of the generated high resolution images (10,400 lines x 7,500 pixel).
Autonomous and integrated passenger and freight transport (APFIT) is a promising approach to tackle both, traffic and last-mile-related issues such as environmental emissions, social and spatial conflicts or operational inefficiencies. By conducting an agent-based simulation, we shed light on this widely unexplored research topic and provide first indications regarding influential target figures of such a system in the rural area of Sarstedt, Germany. Our results show that larger fleets entail inefficiencies due to suboptimal utilization of monetary and material resources and increase traffic volume while higher amounts of unused vehicles may exacerbate spatial conflicts. Nevertheless, to fit the given demand within our study area, a comparatively large fleet of about 25 vehicles is necessary to provide reliable service, assuming maximum passenger waiting times of six minutes to the expense of higher standby times, rebalancing effort, and higher costs for vehicle acquisition and maintenance.
At University of Applied Sciences and Arts Hannover, LON-CAPA is used as a learning management system beside Moodle. LON-CAPA has a strong focus on e-assessment in mathematics and sciences. We used LON-CAPA in Hannover mainly in mathematics courses.
Since theoretical computer science needs a lot of mathematics, this course is also well-suited for e-assessment in LON-CAPA. Beside this, we already used JFLAP as an interactive tool to deal with automata, machines and grammars in theoretical computer science. In LON-CAPA, there exists a possibility of using external graders to grade problems.
We decided to write a grading engine (with JFLAP inside) to grade automata, machines and grammars handed in by students and to couple this with LON-CAPA. This report describes the types of questions that are now possible with this grader and how they can be authored in LON-CAPA.
The bio-based plastic market is forecast to grow in the next years. With a growing market share and product range, the implementation of circular thinking is becoming more and more important also for bio-based plastics to enable a sound circular economy for these group of plastics. Therefore, it is important to assess the environmental performance for different end-of-life options of bio-based plastics from an early stage on. This review presents a comprehensive overview on the current status quo of different end-of-life options for bio-based plastics from an environmental perspective. Based on the status quo and the corresponding impact assessment results, the global plastic demand as well as the technical substitution potential of bio-based plastics, the environmental saving potential in case of the different end-of-life options was calculated. The review shows that there is a focus on polylactic acid (PLA) regarding end-of-life assessment, with studies covering all end-of-life options. The focus of the impact assessment has been set on global warming potential (GWP). With respect to GWP, the analysis of a future global potential of PLA showed, for mechanical recycling, the highest saving potential with 94.1 Mio. t CO2-eq. per year in comparison to virgin material.
The technical, environmental and economic potential of hemp fines as a natural filler in bioplastics to produce biocomposites is the subject of this study – giving a holistic overview. Hemp fines are an agricultural by-product of the hemp fibres and shives production. Shives and fibres are for example used in the paper, animal bedding or composite area. About 15 to 20 wt.-% per kg hemp straw results in hemp fines after processing. In 2010 about 11,439 metric tons of hemp fines were produced in Europe. Hemp fines are an inhomogeneous material which includes hemp dust, shives and fibre. For these examinations the hemp fines are sieved in a further step with a tumbler sieving machine to obtain more specified fractions. The untreated hemp fines (ex work) as well as the sieved fractions are combined with a polylactide polymer (PLA) using a co-rotating twin screw extruder to produce biocomposites with different hemp fine content. By using an injection moulding machine standard test bars are produced to conduct several material tests. The Young’s modulus is increased and the impact strength reduced by hemp fines. With a content of above 15 wt.-% hemp fines are also improving the environmental (global warming potential) and economic performance in comparison to pure PLA.
A novel method has been implemented to prepare metal oxide nanopowders covered with known quantities of adsorbed water; we subsequently studied the γ-radiolysis of ZrO2 nanopowders covered with H2O layers. H2 yields from the adsorbed water radiolysis are of importance in multiple industrial contexts – the nuclear industry being a prime example. Measured H2 yields at water coverages of just below and above one monolayer are around 350 times greater than for neat water, but these yields decrease rapidly with increasing water loading of the ZrO2 nanoparticles, approaching the yield of bulk water at coverages of tens of water layers. The observed plateau of the yields at 0.5 to 2.0 monolayers coverage can be explained by the ease with which electronic excitations in the ZrO2 can be transferred across the interface to the first one or two adsorbed water layers. However, with increasing water loading, energy transfer to water layers further away from the interface becomes less efficient, and above ~30 water layers, most of the water is not affected by any exciton formation in the ZrO2.
Complications may occur after a liver transplantation, therefore proper monitoring and care in the post-operation phase plays a very important role. Sometimes, monitoring and care for patients from abroad is difficult due to a variety of reasons, e.g., different care facilities. The objective of our research for this paper is to design, implement and evaluate a home monitoring and decision support infrastructure for international children who underwent liver transplant operation. A point-of-care device and the PedsQL questionnaire were used in patients’ home environment for measuring the blood parameters and assessing quality of life. By using a tablet PC and a specially developed software, the measured results were able to be transmitted to the health care providers via internet. So far, the developed infrastructure has been evaluated with four international patients/families transferring 38 records of blood test. The evaluation showed that the home monitoring and decision support infrastructure is technically feasible and is able to give timely alarm in case of abnormal situation as well as may increase parent’s feeling of safety for their children.
The ability to functionalize graphene with several methods, such as radical reactions, cycloadditions, hydrogenation, and oxidations, allows this material to be used in a large range of applications. In this framework, it is essential to be able to control the efficiency and stability of the functionalization process—this requires understanding how the graphene reactivity is affected by the environment, including the substrate. In this work we provide an insight on the substrate dependence of graphene reactivity towards hydrogenation by comparing three different substrates: silicon, hexagonal boron nitride (h-BN), and molybdenum disulfide (MoS2). Although MoS2 and h-BN have flatter surfaces than silicon, we found that the H coverage of graphene on h-BN is about half of the H coverage on graphene on both silicon and MoS2. Therefore, graphene shows strongly reduced reactivity towards hydrogenation when placed on h-BN. The difference in hydrogenation reactivity between h-BN and MoS2 may indicate a stronger van der Waals force between graphene and h-BN, compared to MoS2, or may be related to the chemical properties of MoS2, which is a well-known catalyst for hydrogen evolution reactions.
This paper summarizes the results of a comprehensive statistical analysis on a corpus of open access articles and contained figures. It gives an insight into quantitative relationships between illustrations or types of illustrations, caption lengths, subjects, publishers, author affiliations, article citations and others.
The NOA project collects and stores images from open access publications and makes them findable and reusable. During the project a focus group workshop was held to determine whether the development is addressing researchers’ needs. This took place before the second half of the project so that the results could be considered for further development since addressing users’ needs is a big part of the project. The focus was to find out what content and functionality they expect from image repositories.
In a first step, participants were asked to fill out a survey about their images use. Secondly, they tested different use cases on the live system. The first finding is that users have a need for finding scholarly images but it is not a routine task and they often do not know any image repositories. This is another reason for repositories to become more open and reach users by integrating with other content providers. The second finding is that users paid attention to image licenses but struggled to find and interpret them while also being unsure how to cite images. In general, there is a high demand for reusing scholarly images but the existing infrastructure has room to improve.
Background
Maternal postpartum depression has an impact on mother-infant interaction. Mothers with depression display less positive affect and sensitivity in interaction with their infants compared to non-depressed mothers. Depressed women also show more signs of distress and difficulties adjusting to their role as mothers than non-depressed women. In addition, depressive mothers are reported to be affectively more negative with their sons than with daughters.
Methods
A non-clinical sample of 106 mother-infant dyads at psychosocial risk (poverty, alcohol or drug abuse, lack of social support, teenage mothers and maternal psychic disorder) was investigated with EPDS (maternal postpartum depressive symptoms), the CARE-Index (maternal sensitivity in a dyadic context) and PSI-SF (maternal distress). The baseline data were collected when the babies had reached 19 weeks of age.
Results
A hierarchical regression analysis yielded a highly significant relation between the PSI-SF subscale "parental distress" and the EPDS total score, accounting for 55% of the variance in the EPDS. The other variables did not significantly predict the severity of depressive symptoms. A two-way ANOVA with "infant gender" and "maternal postpartum depressive symptoms" showed no interaction effect on maternal sensitivity.
Conclusions
Depressive symptoms and maternal sensitivity were not linked. It is likely that we could not find any relation between both variables due to different measuring methods (self-reporting and observation). Maternal distress was strongly related to maternal depressive symptoms, probably due to the generally increased burden in the sample, and contributed to 55% of the variance of postpartum depressive symptoms.
Background:
This study examined the extent to which regulatory problems in infants at 4 and 6 months influence childhood development at 12 months. The second aim of the study was to examine the influence maternal distress has on 4-month-old children’s subsequent development as well as gender differences with regard to regulatory problems and development.
Methods:
153 mother-child dyads enrolled in the family support research project “Nobody slips through the net” constituted the comparison group. These families faced psychosocial risks (e.g. poverty, excessive demands on the mother, and mental health disorders of the mother, measured with the risk screening instrument Heidelberger Belastungsskala - HBS) and maternal stress, determined with the Parental Stress Index (PSI-SF). The children’s developmental levels and possible early regulatory problems were evaluated by means of the Ages and Stages Questionnaires (ASQ) and a German questionnaire assessing problems of excessive crying along with sleeping and feeding difficulties (SFS).
Results:
A statistically significant but only low, inverse association between excessive crying, whining and sleep problems at 4 and 6 months and the social development of one-year-olds (accounting for 5% and 8% of the variance respectively) was found. Feeding problems had no effect on development. Although regulatory problems in infants were accompanied by increased maternal stress level, these did not serve as a predictor of the child’s social development at 12 months. One-year-old girls reached a higher level of development in social and fine motor skills. No gender differences were found with regard to regulatory problems, nor any moderating effect of gender on the relation between regulatory problems and level of development.
Conclusions:
Our results reinforce existing knowledge pertaining to the transactional association between regulatory problems in infants, maternal distress and dysfunctionality of mother-child interactions. They also provide evidence of a slight but distinct negative influence of crying and sleeping problems on children’s subsequent social development. Easily accessible support services provided by family health visitors (particularly to the so-called “at-risk families”) are strongly recommended to help prevent the broadening of children’s early regulatory problems into other areas of behavior.
This feasibility study investigates the flexural properties of biocomposites containing woven flax textiles (plain, twill, satin) and woven twill patterned hybrid textiles containing flax-/glass or flax-/carbon mixture for lightweight applications. Synthetic fibers are integrated as weft and flax fibers are integrated as warp yarns using a double-rapier weaving machine with a Jacquard attachment. The corresponding biocomposites are manufactured via vacuum infusion process using a biobased epoxy resin as a matrix. The manufactured biocomposites are analyzed with regard to their density and flexural properties. The results show that the use of hybrid textiles offers a promising solution for the manufacture of biocomposites with a higher biobased content and significantly improved flexural properties. Furthermore, the introduction of high-performance synthetic fibers in textiles enables the manufacture of biocomposites with an isotropic mechanical performance.
Food protein hydrolysates are often produced in unspecific industrial batch processes. The hydrolysates composition underlies process-related fluctuations and therefore the obtained peptide fingerprint and bioactive properties may vary. To overcome this obstacle and enable the production of specific hydrolysates with selected peptides, a ceramic capillary system was developed and characterized for the continuous production of a consistent peptide composition. Therefore, the protease Alcalase was immobilized on the surface of aminosilane modified yttria stabilized zirconia capillaries with a pore size of 1.5 μm. The loading capacity was 0.3 μg enzyme per mg of capillary with a residual enzyme activity of 43%. The enzyme specific peptide fingerprint produced with this proteolytic capillary reactor system correlated with the degree of hydrolysis, which can be controlled over the residence time by adjusting the flow rate. Common food proteins like casein, sunflower and lupin protein isolates were tested for continuous hydrolysis in the developed reactor system. The peptide formation was investigated by high-performance liquid chromatography. Various trends were found for the occurrence of specific peptides. Some are just intermediately occurring, while others cumulate by time. Thus, the developed continuous reactor system enables the production of specific peptides with desired bioactive properties.
Introduction: Piper crocatum Ruiz & Pav (P. crocatum) has been reported to accelerate the diabetic wound healing process empirically. Some studies showed the benefits of P. crocatum in treating various diseases but its mechanisms in diabetic wound healing have never been reported. In the present study we investigated the diabetic wound healing activity of the active fraction of P. crocatum on wounded hyperglycemia fibroblasts (wHFs).
Methods: Bioassay-guided fractionation was performed to get the most active fraction. The selected active fraction was applied to wHFs within 72 h incubation. Mimicking a diabetic condition was done using basal glucose media containing an additional 17 mMol/L D-glucose. A wound was simulated via the scratch assay. The collagen deposition was measured using Picro-Sirius Red and wound closure was measured using scratch wound assay. Underlying mechanisms through p53, aSMA, SOD1 and Ecadherin were measured using western blotting.
Results: We reported that FIV is the most active fraction of P. crocatum. We confirmed that FIV\(7.81 mg/ml, 15.62 mg/ml, 31.25 mg/ml, 62.5 mg/ml, and 125 mg/ml) induced the collagen deposition and wound closure of wHFs. Furthermore, FIV treatment (7.81 mg/ml, 15.62 mg/ml, 31.25 mg/ml) down-regulated the protein expression level of p53 and up-regulated the protein expression levels of aSMA, E-cadherin, and SOD1.
Discussion/conclusions: Our findings suggest that ameliorating collagen deposition and wound closure through protein regulation of p53, aSMA, E-cadherin, and SOD1 are some of the mechanisms by which FIV of P. crocatum is involved in diabetic wound healing therapy.
During the transition from conventional towards purely electrical, sustainable mobility, transitional technologies play a major part in the task of increasing adaption rates and decreasing range anxiety. Developing new concepts to meet this challenge requires adaptive test benches, which can easily be modified e.g. when progressing from one stage of development to the next, but also meet certain sustainability demands themselves.
The system architecture presented in this paper is built around a service-oriented software layer, connecting a modular hardware layer for direct access to sensors and actuators to an extensible set of client tools. Providing flexibility, serviceability and ease of use, while maintaining a high level of reusability for its constituent components and providing features to reduce the required overall run time of the test benches, it can effectively decrease the CO2 emissions of the test bench while increasing its sustainability and efficiency.
Cloud computing has become well established in private and public sector projects over the past few years, opening ever new opportunities for research and development, but also for education. One of these opportunities presents itself in the form of dynamically deployable, virtual lab environments, granting educational institutions increased flexibility with the allocation of their computing resources. These fully sandboxed labs provide students with their own, internal network and full access to all machines within, granting them the flexibility necessary to gather hands-on experience with building heterogeneous microservice architectures. The eduDScloud provides a private cloud infrastructure to which labs like the microservice lab outlined in this paper can be flexibly deployed at a moment’s notice.
Context: Higher education is changing at an accelerating pace due to the widespread use of digital teaching and emerging technologies. In particular, AI assistants such as ChatGPT pose significant challenges for higher education institutions because they bring change to several areas, such as learning assessments or learning experiences.
Objective: Our objective is to discuss the impact of AI assistants in the context of higher education, outline possible changes to the context, and present recommendations for adapting to change.
Method: We review related work and develop a conceptual structure that visualizes the role of AI assistants in higher education.
Results: The conceptual structure distinguishes between humans, learning, organization, and disruptor, which guides our discussion regarding the implications of AI assistant usage in higher education. The discussion is based on evidence from related literature.
Conclusion: AI assistants will change the context of higher education in a disruptive manner, and the tipping point for this transformation has already been reached. It is in our hands to shape this transformation.
Coaxial Laser wire Direct Energy Deposition (L-DED) promises a direction-independent buildup due to a centric supply of the welding material. To fabricate Functionally Graded Materials (FGMs), a processing head was designed that is capable of supplying two wire materials into the processing zone. This study investigates the direction dependency of welding seams produced by two 1.4718 metal wires with a diameter of 0.8 mm in a coaxial laser setup using three separately controllable single laser beams with a maximum combined laser power of 660 W. The welding wires are supplied simultaneously to the laser spot under an incidence angle of 3.5° to the middle axis of the processing head. The seam geometry is investigated using a confocal laserscanning-microscope. A comparison of the height, width and macroscopic seam geometry reveals the influence of the welding direction on the seam geometry and quality in Laser Double wire Direct Energy Deposition (LD-DED).
The paper sheds light on the change in the concept of obedience within the Society of Jesus since the 1960s. In the aftermath of the Second Vatican Council, a so-called crisis of authority and obedience took place in the Catholic Church and the religious orders. As a consequence, the notions of responsibility and conscience came to the fore in the Jesuit definition of obedience. The religious concept of obedience, that is the obedience towards God, was reassessed as a service to humanity. The paper analyzes how the change in the concept of obedience gave rise to the promotion of social justice, which the Society of Jesus proclaimed at General Congregation 32 in 1974/75. By including the promotion of social justice into their central mission, Jesuits not only fundamentally transformed their self-conception, but also their ethical values. The paper argues that the pursuit of social justice became a form of religious obedience.
In this paper, we present a novel approach for real-time rendering of soft eclipse shadows cast by spherical, atmosphereless bodies. While this problem may seem simple at first, it is complicated by several factors. First, the extreme scale differences and huge mutual distances of the involved celestial bodies cause rendering artifacts in practice. Second, the surface of the Sun does not emit light evenly in all directions (an effect which is known as limb darkening). This makes it impossible to model the Sun as a uniform spherical light source. Finally, our intended applications include real-time rendering of solar eclipses in virtual reality, which require very high frame rates. As a solution to these problems, we precompute the amount of shadowing into an eclipse shadow map, which is parametrized so that it is independent of the position and size of the occluder. Hence, a single shadow map can be used for all spherical occluders in the Solar System. We assess the errors introduced by various simplifications and compare multiple approaches in terms of performance and precision. Last but not least, we compare our approaches to the state-of-the-art and to reference images. The implementation has been published under the MIT license.
The control of clinical mastitis on dairy farms is an essential part of animal health management. Knowledge of the causative microorganisms, the cure rates achievable in the field and essential associated factors are crucial for proper control. The objectives of the present study were to characterize clinical mastitis cases in Germany and to analyze factors influencing cure rates and the recurrence rate. Milk samples of every clinical mastitis case occurring on 12 participating farms were examined cytomicrobiologically. Post-treatment quarter samples were taken after 14 and 21 days. Treatments were performed according to existing farm protocols. Of 2883 clinical mastitis cases, the most prevalent pathogens were Streptococcus (S.) uberis (20.2%) and coliforms (11.6%). In 35% of the milk samples, no bacteriological growth was detected. The overall bacteriological cure rate was 73.3%, while the cytological cure rate was 22.3%, the full cure rate 21.4% and the recurrence rate 18.8%. Regarding the pathogen distribution of severe mastitis, coliform bacteria were detected in 30.5% of the cases, whereas S. uberis was detected in 26.5% thereof. The results show that severe mastitis is caused almost as frequently by Gram-positive as by Gram-negative microorganisms. The low cytological cure rates show that the therapy needs to be further developed with regard to calming the inflammation. The obtained data can be very helpful in assessing internal mastitis scenarios and the effect of measures and therapies.
Electrospinning with consequent thermal treatment consists in a carbon fiber production method that spins a polymer solution to create fibers with diameters around a few hundred nanometers. The thermal treatments are used for the cyclization and then carbonization of the material at 1700 °C for one hour. The unique structure of micro- and nano-carbon fibers makes them a promising material for various applications ranging from future battery designs to filtration. This work investigated the possibility of using milled gasification biochar, derived from a 20 kW fixed-bed gasifier fueled with vine pruning pellets, as an addictive in the preparation of electrospinning solutions. This study outlined that solvent cleaning and the consequent wet-milling and 32 µm sifting are fundamental passages for biochar preparation. Four different polyacrylonitrile-biochar shares were tested ranging from pure polymer to 50–50% solutions. The resulting fibers were analyzed via scanning electron microscopy, and energy-dispersive X-ray and infrared spectroscopy. Results from the morphological analysis showed that biochar grains dispersed themselves well among the fiber mat in all the proposed shares. All the tested solutions, once carbonized, exceeded 97%wt. of carbon content. At higher carbonization temperatures, the inorganic compounds naturally showing in biochar such as potassium and calcium disappeared, resulting in an almost carbon-pure fiber matrix with biochar grains in between.
Introduction
Atopic dermatitis (AD) is a common inflammatory skin disease. Many patients are initiating a systemic therapy, if the disease is not adequately controlled with topical treatment only. Currently, there is little real-world evidence on the AD-related medical care situation in Germany. This study analyzed patient characteristics, treatment patterns, healthcare resource utilization and costs associated with systemically treated AD for the German healthcare system.
Methods
In this descriptive, retrospective cohort study, aggregated anonymized German health claims data from the InGef research database were used. Within a representative sample of four million insured individuals, patients with AD and systemic drug therapy initiation (SDTI) in the index year 2017 were identified and included into the study cohort. Systemic drug therapy included dupilumab, systemic corticosteroids (SCS) and systemic immunosuppressants (SIS). Patients were observed for one year starting from the date of SDTI in 2017.
Results
9975 patients were included (57.8% female, mean age 39.6 years [SD 25.5]). In the one-year observation period, the most common systemic drug therapy was SCS (> 99.0%). Administrations of dupilumab (0.3%) or dispensations of SIS were rare (cyclosporine: 0.5%, azathioprine: 0.6%, methotrexate: 0.1%). Median treatment duration of SCS, cyclosporine and azathioprine was 27 days, 102 days, and 109 days, respectively. 2.8% of the patients received phototherapy; 41.6% used topical corticosteroids and/or topical calcineurin inhibitor. Average annual costs for medications amounted to € 1237 per patient. Outpatient services were used by 99.6% with associated mean annual costs of € 943; 25.4% had at least one hospitalization (mean annual costs: € 5836). 5.3% of adult patients received sickness benefits with associated mean annual costs of € 5026.
Conclusions
Despite unfavorable risk–benefit profile, this study demonstrated a common treatment with SCS, whereas other systemic drug therapy options were rarely used. Furthermore, the results suggest a substantial economic burden for patients with AD and SDTI.
This paper proposes an extended Petri net formalism as a suitable language for composing optimal scheduling problems of industrial production processes with real and binary decision variables. The proposed approach is modular and scalable, as the overall process dynamics and constraints can be collected by parsing of all atomic elements of the net graph. To conclude, we demonstrate the use of this framework for modeling the moulding sand preparation process of a real foundry plant.
Background:
The increase in food intolerances poses a burgeoning problem in our society. Food intolerances not only lead to physical impairment of the individual patient but also result in a high socio-economic burden due to factors such as the treatment required as well as absenteeism. The present study aimed to explore whether lactose intolerant (LI) patients exhibit more frequent comorbidities than non-LI patients.
Methods:
The study was conducted on a case-control basis and the results were determined using routine data analysis. Routine data from the IMS Disease Analyzer database were used for this purpose. A total of 6,758 data records were processed and analyzed.
Results:
There were significant correlations between LI and the incidence of osteoporosis, changes in mental status, and the presence of additional food intolerances. Comparing 3,379 LI vs. 3,379 non-LI patients, 34.5% vs. 17.7% (P<0.0001) suffered from abdominal pain; 30.6% vs. 17.2% (P<0.0001) from gastrointestinal infections; and 20.9% vs. 16.0% (P=0.0053) from depression. Adjusted odds ratios (OR) were the highest for fructose intolerance (n=229 LI vs. n=7 non-LI; OR 31.06; P<0.0001), irritable bowel syndrome (n=247 LI vs. n=44 non-LI; OR 5.23; P<0.0001), and bloating (n=351 LI vs. n=68 non-LI; OR 4.94; P<0.0001).
Conclusion:
The study confirms that LI should not be regarded as an isolated illness but considered a possible trigger for further diseases. Additional research is necessary to assert more precise statements.
During machine milking, pathogenic microorganisms can be transmitted from cow to cow through liners. Therefore, in Germany, a spray method for the intermediate disinfection of the milking cluster is often used for prevention. This method of cluster disinfection is easy to perform, requires little time and no extra materials, and the disinfection solution is safe from outside contamination in the spray bottle. Since no data on a systematic efficacy trial are available, the aim of this study was to determine the microbial reduction effect of intermediate disinfection. Therefore, laboratory and field trials were conducted. In both trials, two sprays of 0.85 mL per burst of different disinfectant solutions were sprayed into the contaminated liners. For sampling, a quantitative swabbing method using a modified wet–dry swab (WDS) technique based on DIN 10113-1: 1997-07 was applied. Thus, the effectiveness of disinfectants based on Peracetic Acid, Hydrogen Peroxide and Plasma-Activated Buffered Solution (PABS) was compared. In the laboratory trial, the inner surfaces of liners were contaminated with pure cultures of Escherichia (E.) coli, Staphylococcus (S.) aureus, Streptococcus (Sc.) uberis and Sc. agalactiae. The disinfection of the contaminated liners with the disinfectants resulted in a significant reduction in bacteria with values averaging 1 log for E. coli, 0.7 log for S. aureus, 0.7 log for Sc. uberis and 0.8 log for Sc. agalactiae. The highest reduction was obtained for contamination with E. coli (1.3 log) and Sc. uberis (0.8 log) when PABS was applied and for contamination with S. aureus (1.1 log) and Sc. agalactiae (1 log) when Peracetic Acid Solution (PAS) was used. Treatment with sterile water only led to an average reduction of 0.4 log. In the field trial, after the milking of 575 cows, the liners were disinfected and the total microorganism count from the liner surface was performed. The reduction was measured against an untreated liner within the cluster. Although a reduction in microorganisms was achieved in the field trial, it was not significant. When using PAS, a log reduction of 0.3 was achieved; when using PABS, a log reduction of 0.2 was obtained. The difference between the two disinfection methods was also not significant. Treatment with sterile water only led to a reduction of 0.1 log. The results show that spray disinfection under these circumstances does result in a reduction in the bacteria on the milking liner surface, but for effective disinfection a higher reduction would be preferred.
Background: Epidemiological and experimental studies suggest that exposure to ultrafine particles (UFP) might aggravate the allergic inflammation of the lung in asthmatics.
Methods: We exposed 12 allergic asthmatics in two subgroups in a double-blinded randomized cross-over design, first to freshly generated ultrafine carbon particles (64 μg/m3; 6.1 ± 0.4 × 105 particles/cm3 for 2 h) and then to filtered air or vice versa with a 28-day recovery period in-between. Eighteen hours after each exposure, grass pollen was instilled into a lung lobe via bronchoscopy. Another 24 hours later, inflammatory cells were collected by means of bronchoalveolar lavage (BAL). (Trial registration: NCT00527462)
Results: For the entire study group, inhalation of UFP by itself had no significant effect on the allergen induced
inflammatory response measured with total cell count as compared to exposure with filtered air (p = 0.188). However, the subgroup of subjects, which inhaled UFP during the first exposure, exhibited a significant increase in total BAL cells (p = 0.021), eosinophils (p = 0.031) and monocytes (p = 0.013) after filtered air exposure and subsequent allergen challenge 28 days later. Additionally, the potential of BAL cells to generate oxidant radicals was
significantly elevated at that time point. The subgroup that was exposed first to filtered air and 28 days later to UFP did not reveal differences between sessions.
Conclusions: Our data demonstrate that pre-allergen exposure to UFP had no acute effect on the allergic inflammation. However, the subgroup analysis lead to the speculation that inhaled UFP particles might have a long-term effect on the inflammatory course in asthmatic patients. This should be reconfirmed in further studies with an appropriate study design and sufficient number of subjects.
The objective was to establish and standardise a broth microdilution susceptibility testing method for porcine Bordetella (B.) bronchiseptica. B. bronchiseptica isolates from different geographical regions and farms were genotyped by macrorestriction analysis and subsequent pulsed-field gel electrophoresis. One reference and one type strain plus two field isolates of B. bronchiseptica were chosen to analyse growth curves in four different media: cation-adjusted Mueller-Hinton broth (CAMHB) with and without 2% lysed horse blood, Brain-Heart-Infusion (BHI), and Caso broth. The growth rate of each test strain in each medium was determined by culture enumeration and the suitability of CAMHB was confirmed by comparative statistical analysis. Thereafter, reference and type strain and eight epidemiologically unrelated field isolates of B. bronchiseptica were used to test the suitability of a broth microdilution susceptibility testing method following CLSI-approved performance standards given in document VET01-A4. Susceptibility tests, using 20 antimicrobial agents, were performed in five replicates, and data were collected after 20 and 24 hours incubation and statistically analysed. Due to the low growth rate of B. bronchiseptica, an incubation time of 24 hours resulted in significantly more homogeneous minimum inhibitory concentrations after five replications compared to a 20-hour incubation. An interlaboratory comparison trial including susceptibility testing of 24 antimicrobial agents revealed a high mean level of reproducibility (97.9%) of the modified method. Hence, in a harmonization for broth microdilution susceptibility testing of B. bronchiseptica, an incubation time of 24 hours in CAMHB medium with an incubation temperature of 35°C and an inoculum concentration of approximately 5 x 105 cfu/ml was proposed.