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Abstract Introduction This pilot study investigated the effects of a 12-week administration of a nutritional supplement containing special collagen peptides on the structural and molecular properties of the collagen fiber network in the human skin. For the assessments, the suction blister method and electron microscopical comparisons were used. Methods Three suction blisters were generated on the inner forearm of each test subject before and after the 12-week administration of the nutritional supplement. High-resolution scanning electron microscopy (SEM) was employed to meticulously investigate the structural characteristics of the skin’s collagen network, including the length and diameter of collagen fibers within the suction blister roof. Furthermore, the analysis included immunohistochemistry and fluorescence light microscopy to study hyaluronic acid within the extracellular matrix. Additional assessments encompassed changes in various epidermal parameters. Nine female participants within the age range of 43.7–61.8 years (mean: 52.5 ± 5.9 years) completed the study in accordance with the study protocol. Results Compared with baseline, the 12-week supplementation regimen led to a statistically significant average increase in the collagen fiber network size of 34.56% (p

Vertical farming is considered to be a key enabler for transforming agrifood systems, especially in or nearby urbanized areas. Vertical farming systems (VFS) are advanced indoor cropping systems that allow for highly intensified and standardized plant production. The close control of environmental parameters makes crop production stable and repeatable, ensuring year-round uniform product quality and quantity irrespective of location. However, due to continuous changes in plant physiology and development, as well as frequent changes in electricity prices, the optimum conditions for crop production and its associated costs can change within days or even minutes. This makes it beneficial to dynamically adjust setpoints for light (intensity, spectrum, pattern, and daylength), CO2, temperature, humidity, air flow, and water and nutrient availability. In this review, we highlight the beneficial effects that dynamic growth conditions can have on key plant processes, including improvements in photosynthetic gas exchange, transpiration, organ growth, development, light interception, flowering, and product quality. Our novel findings based on modeling and experimentation demonstrate that a dynamic daily light intensity pattern that responds to frequent changes in electricity prices can save costs without reducing biomass. Further, we argue that a smart, dynamic VFS climate management requires feedback mechanisms: several mobile and immobile sensors could work in combination to continuously monitor the crop, generating data that feeds into crop growth models, which, in turn, generate climate setpoints. In addition, we posit that breeding for the VFS environment is at a very early stage and highlight traits for breeding for this specialized environment. We envision a continuous feedback loop between dynamic crop management, crop monitoring, and trait selection for genotypes that are specialized for these conditions.

The appropriateness of branding certain disaster events as a natural disaster continues to be academically debated, given that few disasters are solely the result of uncontrollable forces of nature, and are instead anthropogenic in their creation, or exacerbated by the relationship humans have with actual and potential hazards. Therefore, this socially constructed nature of disasters also makes groups that are marginalized within society, such as queer people, more vulnerable to these disasters. Utilizing a Bourdieusian framework, the field of disaster preparedness, management, and recovery is examined for queer vulnerability, which is deconstructed here as a product of global and local cultures, in their distribution of economic, social, cultural, and symbolic capital away from queer people. The concepts of habitus and subsidiary concepts of ethos and doxa are deployed to understand the ingrained ways of doing and being that perpetuate discrimination against queer individuals through said inequitable distributions of capital. It is argued that the field is privileged for heteronormative lives, thus leading to heteronormative assumptions and actions that further marginalize queer experiences before, during, and after disasters during disasters. In light of this, we call for a more social justice informed approach to disaster risk reduction and relief, in which heteronormativity is consciously decentered to ensure all groups are kept safe from disasters, which can arguably never be natural.

Abstract Projection imaging accelerates volumetric interrogation in fluorescence microscopy, but for multi-cellular samples, the resulting images may lack contrast, as many structures and haze are summed up. Here, we demonstrate rapid projective light-sheet imaging with parameter selection (props) of imaging depth, position and viewing angle. This allows us to selectively image different sub-volumes of a sample, rapidly switch between them and exclude background fluorescence. Here we demonstrate the power of props by functional imaging within distinct regions of the zebrafish brain, monitoring calcium firing inside muscle cells of moving Drosophila larvae, super-resolution imaging of selected cell layers, and by optically unwrapping the curved surface of a Drosophila embryo. We anticipate that props will accelerate volumetric interrogation, ranging from subcellular to mesoscopic scales.

Abstract Light-sheet fluorescence microscopy has transformed our ability to visualize and quantitatively measure biological processes rapidly and over long time periods. In this review, we discuss current and future developments in light-sheet fluorescence microscopy that we expect to further expand its capabilities. This includes smart and adaptive imaging schemes to overcome traditional imaging trade-offs, i.e., spatiotemporal resolution, field of view and sample health. In smart microscopy, a microscope will autonomously decide where, when, what and how to image. We further assess how image restoration techniques provide avenues to overcome these tradeoffs and how “open top” light-sheet microscopes may enable multi-modal imaging with high throughput. As such, we predict that light-sheet microscopy will fulfill an important role in biomedical and clinical imaging in the future.

From a complexity perspective on governance, multilateral diplomacy is based on interactions between people, ideas, norms, policies and institutions. This article uses a computer-assisted methodology to better understand governance systems as a network of norms. All World Health Assembly (WHA) resolutions that were available from 1948 to 2022 were collected from the WHO Institutional Repository for Information Sharing (IRIS) database. Regular expressions were used to identify how resolutions cite other resolutions and the resulting relationships were analysed as a normative network. The findings show that WHA resolutions constitute a complex network of interconnected global health issues. This network is characterised by several community patterns. While chain-like patterns are associated with specific diseases programmes, radial patterns are characteristic of highly important procedural decisions that member states reaffirm in similar situations. Finally, densely connected communities correspond to contested topics and emergencies. While these emergeng patterns suggest the relevance of using network analysis to understand global health norms in international organisations, we reflect on how this computational approach can be extended to provide new understandings of how multilateral governance systems work, and to address some important contemporary questions about the effects of regime complexity on global health diplomacy.

The mesothelium supports homeostasis and regeneration, yet its development origins remain unclear. Here, the authors uncovered the earliest mesothelium progenitor cells in zebrafish, linking Hand2 gene function to mesothelium formation and its re-activation to mesothelioma tumors.

The ability to visualise stochastic invasion events is limited in murine models of metastatic cancers. Here the authors use a transparent zebrafish epidermis model to follow the invasion events of K-Ras transformed epithelial cells and show that these cells invade through basal cell extrusion.

In the last decade, the German transition system has witnessed the large‐scale introduction of so‐called “analysis of potentials” (Potenzialanalysen) in secondary compulsory schooling. In most German Länder, 8th graders must participate in a two‐day assessment center which combines psychometric testing with observations of their social and professional competencies in pre‐specified tasks. The programmatic aim of these assessments is to “introduce pupils early to choosing a job” (Bundesministerium für Bildung und Forschung [BMBF], 2017, p. 2) as well as to enhance the propensity of pupils to “take responsibility for their own future” (BMBF, 2017, p. 9). In the context of the German school‐to‐work system, the introduction of these new forms of diagnostics bear witness to a new preventive political rationality that aims at reducing the entry age into upper secondary education, reduce the recourse to so‐called “transition measures” and optimizing transitions into an apprenticeship market that is characterized by structural inequalities and “mismatch” between pupils’ job aspirations and the offers in apprenticeship places. However, little is known on the role of competency testing devices for the construction of further trajectories and aspirations and their role in the reproduction of inequalities in transitions from school to work. Based on an in‐depth analysis of policy documents and competency profiles (the documents handed out to the pupils after undergoing testing), the article reconstructs the political rationale for the introduction of the so‐called Potenzialanalysen. Based on a Foucauldian framework, we show how pupils are constructed as “competent” subjects. We show that competency assessments are part and parcel of a political rationality that aims at the promotion of a specific (future‐oriented, optimized, self‐regulated) relation to one’s own biographical future on the side of the pupils. Our results demonstrate that competency profiles construct the process of choosing a job as an individualized project of the self and that they invisibilize structural barriers and power relations. In doing so, competency assessments potentially contribute to the reproduction of inequalities in post‐secondary education through delegating “cooling out” processes from institutional gatekeepers to the interiority of persons.

Epidermal barrier dysfunction can lead to xerotic skin and promote skin disorders like atopic dermatitis. Atopic skin is characterized by reduced water-retaining compounds, altered lipid composition and elevated skin pH. Against this background, a study was conducted to investigate the impact of a specific skin care product on epidermal barrier function in dry and atopic-prone skin. A marketed pH 4.5 cosmetic formulation containing 10% urea and specific plant oils was evaluated on 25 subjects with dry and atopic-prone skin. Measurements of skin hydration, pH, and barrier function were performed before and after 3 weeks of product usage. Additionally, visual scoring and stratum corneum lipid analysis using electron microscopy were conducted to investigate lipid composition. An improved skin hydration compared to the untreated area and a tendency to decrease the baseline elevated skin surface pH were observed. The visual scoring showed reduced dryness, roughness, and tension through the application. Furthermore, the stratum corneum lipid matrix was improved in terms of lipid content and organization. The combination of an acidic product’s pH, a relevant urea content and effective plant oils is shown to be beneficial in terms of improving the skin barrier function, structure and appearance and is recommended for dry and atopic-prone skin.

Abstract Background Surgical site infections (SSI) are rare but severe complications after total joint arthroplasty (TJA). Decolonization measures prior to elective orthopedic surgeries have shown to reduce the risk of SSI with Staphylococcus aureus (S. aureus). Objective To determine the efficacy of universal decolonization with Polyhexanide on SSI rates with a focus on Staphylococcus aureus in patients with TJA. Methods Patients scheduled for elective hip or knee TJA in 5 participating certified orthopedic centers were included between 2015 and 2018 into this before and after study. Data on patients, surgeries and infections were prospectively collected. CDC-criteria were used to define and categorize Infections within 90 days after surgery. From January 2017 on, patients received decolonization sets containing Polyhexanide. Patients performed a 5 day decolonization regimen starting 4 days prior to surgery which included wipes, nasal decontamination and oral solution. Results Thirteen thousand, three hundred fifteen patients received TJA. During intervention 4437 decolonization sets were distributed among 7175 patients. Overall SSI rates increased from 0.68 /100 surgeries to 0.91/ 100 surgeries after implementation of the intervention (IRR 1.32; 95% CI 0.90–1.96). Time series analysis identified an increasing trend of SSI prior to the intervention. After implementation overall SSI rates plateaued. Regression analysis revealed surgery during intervention period to be an independent risk factor for developing a SSI (OR 1.34; 95%CI 1.18–1.53). Initial SSI rates due to S. aureus were 0.24/100 surgeries and decreased to 0.14/100 surgeries (IRR 0.57; 95% CI 0.25–1.22) after introduction of decolonization. Regression analysis revealed surgery during intervention period to be an independent protective factor for developing a SSI with S. aureus (OR 0.57, 95% CI: 0.33–0.99). Overall deep S. aureus SSI decreased significantly from 0.22/100 surgeries to 0.00/100 surgeries in patients adherent to protocol (IRR 0.00, 95% CI 0.00–.85). Conclusion Universal decolonization with Polyhexanide did not reduce overall surgical site infections, but was effective in reducing Staphylococcus aureus - surgical site infections following elective joint arthroplasty. Polyhexanide could extend the list of alternatives to already established decolonization strategies. Trial registration The trial was registered at the German Registry for clinical studies www.drks.de ( DRKS00011505 ).

Nummular (coin-shaped) and classical (flexural) atopic dermatitis differ morphologically, but no other distinguishing features are known. The aim of this study was to determine differences and similarities of both variants in children. Detailed interviews, clinical examinations, biophysical measurements and electron microscopic analyses were performed on 10 children with nummular atopic dermatitis, 14 with classical atopic dermatitis and 10 healthy controls. Nummular atopic dermatitis affected more boys than girls and manifested less frequently within the first year of life than classical atopic dermatitis. Localization, distribution and morphology of the eczema varied more over time, and expression of keratosis pilaris was more severe in children with nummular atopic dermatitis. Both disease groups showed reduced hydration, increased transepidermal water loss and reduced intercellular lipid lamellae in lesional skin areas compared with non-lesional areas. These findings underline the separate classification of both variants. Further research is necessary to investigate the potential of diverging therapeutic approaches.

Reproducing computational workflows in image analysis and microscopy can be a daunting task due to different software versions and dependencies. This is especially true for users with little specific knowledge of scientific computation. To overcome these challenges, we introduce Singularity containers as a useful tool to run and share image analysis workflows among many users, even years later after establishing them. Unfortunately, containers are rarely used so far in the image analysis field. To address this lack of use, we provide a detailed step-by-step protocol to package a state-of-the-art segmentation algorithm into a container on a local Windows machine to run the container on a high-performance cluster computer.

The COVID-19 healthcare crisis dramatically changed educational opportunities for undergraduate students. To overcome the lack of exposure to lab research and provide an alternative to cancelled classes and online lectures, the Lyda Hill Department of Bioinformatics at UT Southwestern Medical Center established an innovative, fully remote and paid “U-Hack Med Gap Year” internship program. At the core of the internship program were dedicated biomedical research projects spanning nine months in fields as diverse as computational microscopy, bioimage analysis, genome sequence analysis and establishment of a surgical skill analysis platform. To complement the project work, a biweekly Gap Year lab meeting was devised with opportunities to develop important skills in presenting, data sharing and analysis of new research. Despite a challenging year, all selected students completed the full internship period and over 30% will continue their project remotely after the end of the program.

Annotation of time-lapse data provides an important tool to highlight dynamic processes. Particularly, arrows, circles and arrowheads are useful to pinpoint a specific process, stationary or evolving over time. Here, we describe a user-friendly Fiji plugin to facilitate annotation of movies with arrows, arrowheads and circles. The plugin also enables saving and loading of annotated tracks. This article has an associated First Person interview with the first author of the paper.

Efficient chemical modification of cellulose nanocrystals (CNCs) by grafting commonly involves aprotic solvents, toxic reactants, harsh reaction conditions, or catalysts, which have negative effects on the particle character, reduced dispersibility and requires further purification, if products are intended for biomedical applications. This work, in contrast, presents a robust, facile, and green synthesis protocol for the grafting of an amino-reactive fluorophore like fluorescein isothiocyanate (FITC) on aqueous CNCs, combining and modifying existent approaches in a two-step procedure. Comparably high grafting yields were achieved, which were confirmed by thermogravimetry, FTIR, and photometry. The dispersive properties were confirmed by DLS, AF4-MALS, and TEM studies. The presented route is highly suitable for the introduction of silane-bound organic groups and offers a versatile platform for further modification routes of cellulose-based substrates.

Based on an ethnographic study of an activation measure for the young and unemployed, this contribution explores how citizenship is negotiated in frontline interactions and in different elements of activation policies. This article aims to contribute to a deeper understanding of the transformations of citizenship in a welfare service state, characterized by a stricter conditionalization, contractualization, and individualization. It is argued that the transformations of citizenship become distinctively visible in the case of young people on which -as “citizen-worker of the future” (Lister 2003) – a specific political attention is cast. The article discusses the current transformation of citizenship on different levels: firstly, as active citizenship amounts to the promotion of a “desirable self-regulation” (Dean 1995), the focus lies on those practices that institutionalize new expectations to the subjects, namely, that they are to be reflexive and responsible for themselves; secondly, it argues that the paradigmatic transformation toward an active welfare state citizenship confronts SLB´s with a multitude of institutional logics that must be coordinated and compromised on the frontline level. The analysis of “critical incidents” in activation practice shows how the terms and conditions of citizenship are negotiated in contractual integration agreements and in the situated application of sanctions. The practice of activation amounts to an institutionally guided self-exploration that operates with a contradictory mix of client-centered counselling and compulsion. Finally, the implications of the results – particularly for citizenship of the young - are discussed.

The limiting current density is one of to the most important indicators in electroplating for the maximal current density from which a metal can be deposited effectively from an electrolyte. Hence, it is an indicator of the maximal deposition speed and the homogeneity of the thickness of the deposited metal layer. For these reasons, a major interest in the limiting current density is given in practical applications. Usually, the limiting current density is determined via measurements. In this article, a simple model to compute the limiting current density is presented, basing on a system of diffusion–reaction equations in one spatial dimension. Although the model formulations need many assumptions, it is of special interest for screenings, as well as for comparative work, and could easily be adjusted to measurements.

Abstract Background Fair comparisons of educational systems in large-scale assessments can be made only if the differences in curricula have little impact on the outcomes. This study investigated the sensitivity of science achievement rankings to varying degrees of curriculum implementation in the Trends in International Mathematics and Science Study (TIMSS). Methods Country-specific teacher-reported curriculum implementation profiles across the TIMSS science domains were charted including their within-country variability across the classrooms for 33 participating countries of TIMSS 2015. A sensitivity test compared the original ranking to TIMSS curriculum implementation scenarios (a least-possible, a most-possible, and more realistic country-specific median implementation). Results In contrast to expectations, no support was found for a positive relationship between opportunity to learn and science achievement at the between-country level or the within-country level, with only minor exceptions. The sensitivity analysis under different curriculum implementation scenarios also suggests little impact on the rank order of the countries. Conclusions Plausible explanations for this null finding are addressed; attention and research efforts should focus on improving the quality of curriculum implementation indicators in large-scale assessments.

Abstract The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system revolutionized the field of gene editing but viral delivery of the CRISPR/Cas9 system has not been fully explored. Here we adapted clinically relevant high-capacity adenoviral vectors (HCAdV) devoid of all viral genes for the delivery of the CRISPR/Cas9 machinery using a single viral vector. We present a platform enabling fast transfer of the Cas9 gene and gRNA expression units into the HCAdV genome including the option to choose between constitutive or inducible Cas9 expression and gRNA multiplexing. Efficacy and versatility of this pipeline was exemplified by producing different CRISPR/Cas9-HCAdV targeting the human papillomavirus (HPV) 18 oncogene E6, the dystrophin gene causing Duchenne muscular dystrophy (DMD) and the HIV co-receptor C-C chemokine receptor type 5 (CCR5). All CRISPR/Cas9-HCAdV proved to be efficient to deliver the respective CRISPR/Cas9 expression units and to introduce the desired DNA double strand breaks at their intended target sites in immortalized and primary cells.

A deficient epidermal barrier is a key feature of atopic dermatitis (AD) and comprises altered lipid and protein content and composition of the stratum corneum resulting in disturbed water balance. Clinically, eczematous lesions on dry skin and pruritus develop. Pruritic nodules occur in prurigo nodularis (PN), another chronic skin disease, which can be associated with atopy. We aimed at comparing the three clinical pictures, classic AD, atopic prurigo (AP), and non-atopic PN, to healthy controls regarding the epidermal barrier. We determined clinical parameters and performed biophysical measurements, histology/immunohistochemistry, electron microscopy, and molecular biological analysis. We found distinctively elevated clinical scores, reduced hydration and increased transepidermal water loss, epidermal hyperplasia and inflammation reduced filaggrin and increased loricrin and involucrin expression, as well as reduced intercellular lipid lamellae in all three disease groups. These findings show a severe disruption in epidermal barrier structure and function in all three disorders so that epidermal barrier impairment is now proven not only for AD but also for PN.

A better understanding of their interaction with cell-based tissue is a fundamental prerequisite towards the safe production and application of engineered nanomaterials. Quantitative experimental data on the correlation between physicochemical characteristics and the interaction and transport of engineered nanomaterials across biological barriers, in particular, is still scarce, thus hampering the development of effective predictive non-testing strategies. Against this background, the presented study investigated the translocation of gold and silver nanoparticles across the gastrointestinal barrier along with related biological effects using an in vitro 3D-triple co-culture cell model. Standardized in vitro assays and quantitative polymerase chain reaction showed no significant influence of the applied nanoparticles on both cell viability and generation of reactive oxygen species. Transmission electron microscopy indicated an intact cell barrier during the translocation study. Single particle ICP-MS revealed a time-dependent increase of translocated nanoparticles independent of their size, shape, surface charge, and stability in cell culture medium. This quantitative data provided the experimental basis for the successful mathematical description of the nanoparticle transport kinetics using a non-linear mixed effects modeling approach. The results of this study may serve as a basis for the development of predictive tools for improved risk assessment of engineered nanomaterials in the future.

Thermodynamic equilibria and concentrations in thermodynamic equilibria are of major importance in chemistry, chemical engineering, physical chemistry, medicine etc. due to a vast spectrum of applications. E.g., concentrations in thermodynamic equilibria play a central role for the estimation of drug delivery, the estimation of produced mass of products of chemical reactions, the estimation of deposited metal during electro plating and many more. Species concentrations in thermodynamic equilibrium are determined by the system of reactions and to the reactions’ associated stability constants. In many applications the stability constants and the system of reactions need to be determined. The usual way to determine the stability constants is to evaluate titration curves. In this context, many numerical methods exist. One major task in this context is that the corresponding inverse problems tend to be unstable, i.e., the output is strongly affected by measurement errors, and can output negative stability constants or negative species concentrations. In this work an alternative model for the species distributions in thermodynamic equilibrium, based on the models used for HySS or Hyperquad, and titration curves is presented, which includes the positivity of species concentrations and stability constants intrinsically. Additionally, in this paper a stabilized numerical methodology is presented to treat the corresponding model guaranteeing the convergence of the algorithm. The numerical scheme is validated with clinical numerical examples and the model is validated with a Citric acid–Nickel electrolyte. This paper finds a stable, convergent and efficient methodology to compute stability constants from potentiometric titration curves.

Three-component systems of diffusion–reaction equations play a central role in the modelling and simulation of chemical processes in engineering, electro-chemistry, physical chemistry, biology, population dynamics, etc. A major question in the simulation of three-component systems is how to guarantee non-negative species distributions in the model and how to calculate them effectively. Current numerical methods to enforce non-negative species distributions tend to be cost-intensive in terms of computation time and they are not robust for big rate constants of the considered reaction. In this article, a method, as a combination of homotopy methods, modern augmented Lagrangian methods, and adaptive FEMs is outlined to obtain a robust and efficient method to simulate diffusion–reaction models with non-negative concentrations. Although in this paper the convergence analysis is not described rigorously, multiple numerical examples as well as an application to elctro-deposition from an aqueous Cu2+-(β-alanine) electrolyte are presented.

Currently the surgical training of parietal bone graft techniques is performed on patients or specimens. Commercially available bone models do not deliver realistic haptic feedback. Thus customized parietal skull surrogates were developed for surgical training purposes. Two human parietal bones were used as reference. Based on the measurement of insertion forces of drilling, milling and saw procedures suitable material compositions for molding cortical and cancellous calvarial layers were found. Artificial skull caps were manufactured and tested. Additionally microtomograpy images of human and artificial parietal bones were performed to analyze outer table and diploe thicknesses. Significant differences between human and artificial skulls were not detected with the mechanical procedures tested. Highly significant differences were found for the diploe thickness values. In conclusion, an artificial bone has been created, mimicking the properties of human parietal bone thus being suitable for tabula externa graft lift training.

DnaA is a conserved key regulator of replication initiation in bacteria, and is homologous to ORC proteins in archaea and in eukaryotic cells. The ATPase binds to several high affinity binding sites at the origin region and upon an unknown molecular trigger, spreads to several adjacent sites, inducing the formation of a helical super structure leading to initiation of replication. Using FRAP analysis of a functional YFP-DnaA allele in Bacillus subtilis, we show that DnaA is bound to oriC with a half-time of 2.5 seconds. DnaA shows similarly high turnover at the replication machinery, where DnaA is bound to DNA polymerase via YabA. The absence of YabA increases the half time binding of DnaA at oriC, showing that YabA plays a dual role in the regulation of DnaA, as a tether at the replication forks, and as a chaser at origin regions. Likewise, a deletion of soj (encoding a ParA protein) leads to an increase in residence time and to overinitiation, while a mutation in DnaA that leads to lowered initiation frequency, due to a reduced ATPase activity, shows a decreased residence time on binding sites. Finally, our single molecule tracking experiments show that DnaA rapidly moves between chromosomal binding sites, and does not arrest for more than few hundreds of milliseconds. In Escherichia coli, DnaA also shows low residence times in the range of 200 ms and oscillates between spatially opposite chromosome regions in a time frame of one to two seconds, independently of ongoing transcription. Thus, DnaA shows extremely rapid binding turnover on the chromosome including oriC regions in two bacterial species, which is influenced by Soj and YabA proteins in B. subtilis, and is crucial for balanced initiation control, likely preventing fatal premature multimerization and strand opening of DnaA at oriC.

In agricultural production, land-use decisions are components of economic planning that result in the strategic allocation of fields. Climate variability represents an uncertainty factor in crop production. Considering yield impact, climatic influence is perceived during and evaluated at the end of crop production cycles. In practice, this information is then incorporated into planning for the upcoming season. This process contributes to attitudes toward climate-induced risk in crop production. In the literature, however, the subjective valuation of risk is modeled as a risk attitude toward variations in (monetary) outcomes. Consequently, climatic influence may be obscured by political and market influences so that risk perceptions during the production process are neglected. We present a utility concept that allows the inclusion of annual risk scores based on mid-season risk perceptions that are incorporated into field-planning decisions. This approach is exemplified and implemented for winter wheat production in the Kraichgau, a region in Southwest Germany, using the integrated bio-economic simulation model FarmActor and empirical data from the region. Survey results indicate that a profitability threshold for this crop, the level of "still-good yield" (sgy), is 69 dt ha-1 (regional mean Kraichgau sample) for a given season. This threshold governs the monitoring process and risk estimators. We tested the modeled estimators against simulation results using ten projected future weather time series for winter wheat production. The mid-season estimators generally proved to be effective. This approach can be used to improve the modeling of planning decisions by providing a more comprehensive evaluation of field-crop response to climatic changes from an economic risk point of view. The methodology further provides economic insight in an agrometeorological context where prices for crops or inputs are lacking, but farmer attitudes toward risk should still be included in the analysis.

This article identifies the underlying molecular events responsible for fracture nonunions in a subset of fracture patients. Expression profiling of fracture callus tissue from both uneventful fracture repair and nonunion outcomes showed a decrease of COX-2 expression and an inability to mount an immune response in nonunion fractures. Validation in vitro with Saos-2 osteoprogenitor cell lines showed a decrease in osteogenesis potential after the cells were treated with celecoxib, a COX-2 specific inhibitor and anti-inflammatory agent. This article recapitulates that an initial immune response is crucial to fracture healing and suggests limited usage of COX-2 inhibitors in patients with healing fractures. [ABSTRACT FROM AUTHOR]

In developing countries the use of wastewater for irrigation can cause considerable harm to public health and the environment. This paper uses contingent valuation to estimate the economic value of safe use of wastewater for crop production on farms within and around Addis Ababa, Ethiopia. We estimate a surprisingly large welfare gain from policies for safe use of wastewater for irrigation. Our study highlights the potential and the possible pitfalls of using nonmarket valuation techniques as an input into public decision making where traditional resource use interacts with public health and environmental concerns in complex ways.

During embryonic development, vascular networks remodel to meet the increasing demand of growing tissues for oxygen and nutrients. This is achieved by the pruning of redundant blood vessel segments, which then allows more efficient blood flow patterns. Because of the lack of an in vivo system suitable for high-resolution live imaging, the dynamics of the pruning process have not been described in detail. Here, we present the subintestinal vein (SIV) plexus of the zebrafish embryo as a novel model to study pruning at the cellular level. We show that blood vessel regression is a coordinated process of cell rearrangements involving lumen collapse and cell-cell contact resolution. Interestingly, the cellular rearrangements during pruning resemble endothelial cell behavior during vessel fusion in a reversed order. In pruning segments, endothelial cells first migrate toward opposing sides where they join the parental vascular branches, thus remodeling the multicellular segment into a unicellular connection. Often, the lumen is maintained throughout this process, and transient unicellular tubes form through cell self-fusion. In a second step, the unicellular connection is resolved unilaterally, and the pruning cell rejoins the opposing branch. Thus, we show for the first time that various cellular activities are coordinated to achieve blood vessel pruning and define two different morphogenetic pathways, which are selected by the flow environment.

From the mid-nineties on, European welfare states are facing formidable pressures. As a response to these pressures, a strong international reform agenda has found support around the ideas that benefit recipients have to be “activated” in order to find Jobs. Such approaches conceive the aim of welfare states to strengthen Social Policy as a productive factor and to provide the “right” incentives and compulsion (carrots and sticks) in order to control and design behaviour of persons (van Berkel, 2010; Handler, 2004). On an ideological level, these developments correspond to a shift from previously contested assumptions about human motivation, choice, agency and human responsibility of beneficaries of the welfare state. In Critical Social Policy research, a discussion has emerged around the models of human motivation and agency that have been influential in policy design (see e.g. Le Grand, 2003; Deacon, 2005; White, 2013). The article argues that conceptions of human agency have important political implications when it comes to debates about individual responsibility. This may lead to so called “autonomy gaps” (Anderson, 2009), or to situations in which welfare beneficaries perceive the instituionalized imperative to autonomy as an injunction. The article confronts the capability approach (C.A.) to different competing sociological conceptions of human agency. On the basis of an empirical study of the construction of welfare subjects through activation policies, the article points to some shortcomings of the C.A. especially for the analysis of the micro-workings of power in post-disciplinary societies, in which the exercise of power does not so much consist of imposing direct constraints upon citizens as of “governing trough freedom”. For this reason, the article argues that Sen’s realization-based approach needs to be supplemented by concepts which allow accounting for the social mediatedness of individual identities and for the social construction of subjectivity within different social contexts.

This paper is concerned with the analysis and decomposition of medical multichannel data. We present a signal processing technique that reliably detects and separates signal components such as mMCG, fMCG, or MMG by involving the spatiotemporal morphology of the data provided by the multisensor geometry of the so-called multichannel superconducting quantum interference device (SQUID) system. The mathematical building blocks are coorbit theory, multi-α-modulation frames, and the concept of joint sparsity measures. Combining the ingredients, we end up with an iterative procedure (with component-dependent projection operations) that delivers the individual signal components.

Although multiple susceptibility loci for late-onset Alzheimer's disease (LOAD) have been identified, a large portion of the genetic risk for this disease remains unexplained. LOAD risk may be associated with single-nucleotide polymorphisms responsible for changes in gene expression (eSNPs). To detect eSNPs associated with LOAD, we integrated data from LOAD genome-wide association studies and expression quantitative trait loci using Sherlock (a Bayesian statistical method). We identified a cis-regulatory eSNP (rs2927438) located on chromosome 19q13.32, for which subsequent analyses confirmed the association with both LOAD risk and the expression level of several nearby genes. Importantly, rs2927438 may represent an APOE-independent LOAD eSNP according to the weak linkage disequilibrium of rs2927438 with the 2 polymorphisms (rs7412 and rs429358) defining the APOE-ε2, -ε3, and -ε4 alleles. Furthermore, rs2927438 does not influence chromatin interaction events at the APOE locus or cis-regulation of APOE expression. Further exploratory analysis revealed that rs2927438 is significantly associated with tau levels in the cerebrospinal fluid. Our findings suggest that rs2927438 may confer APOE-independent risk for LOAD., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Classical autism or autistic disorder belongs to a group of genetically heterogeneous conditions known as Autism Spectrum Disorders (ASD). Heritability is estimated as high as 90% for ASD with a recently reported compilation of 629 clinically relevant candidate and known genes. We chose to undertake a descriptive next generation whole exome sequencing case study of 30 well-characterized Caucasian females with autism (average age, 7.7 ± 2.6 years; age range, 5 to 16 years) from multiplex families. Genomic DNA was used for whole exome sequencing via paired-end next generation sequencing approach and X chromosome inactivation status. The list of putative disease causing genes was developed from primary selection criteria using machine learning-derived classification score and other predictive parameters (GERP2, PolyPhen2, and SIFT). We narrowed the variant list to 10 to 20 genes and screened for biological significance including neural development, function and known neurological disorders. Seventy-eight genes identified met selection criteria ranging from 1 to 9 filtered variants per female. Five females presented with functional variants of X-linked genes (IL1RAPL1, PIR, GABRQ, GPRASP2, SYTL4) with cadherin, protocadherin and ankyrin repeat gene families most commonly altered (e.g., CDH6, FAT2, PCDH8, CTNNA3, ANKRD11). Other genes related to neurogenesis and neuronal migration (e.g., SEMA3F, MIDN), were also identified.

The era of personalized medicine is upon us and it is being fueled by large available data sets of many types that are setting the foundation for the development of more precise diagnostic tools and targeted therapies, which are improving patient outcomes. Technology innovation and concomitant price decreases in molecular scanning technologies are at the heart of this change, both accelerating at a rate that has exceeded Moore's law. This technology trend is enabling the research community to generate, and make publicly available, massive amounts of genomic data. These data come in the form not only of contextual information about the structure and function of the genome, but also in the form of variants that are correlated with human disease. Coupled with this molecular information, we are making dramatic inroads into capturing and making available high-resolution phenotypic and environmental exposure data through both incentives to physicians to migrate electronic medical records and to adoption of consumer-facing data collection and aggregation technologies. These large-scale genomic, environmental and phenotypic data together allow us to provide a multitude of new diagnostic correlations across the spectrum of possible clinical indications. To fully leverage the data foundation that will lead us to precise diagnostics and truly move the needle in outcome improvement, we need to achieve a culture shift as to how to apply this new personalized and probabilistic diagnostic information to better practice the art of medicine.