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Soil moisture profile sensors (SMPSs) have a high potential for climate-smart agriculture due to their easy handling and ability to perform simultaneous measurements at different depths. To date, an accurate and easy-to-use method for the evaluation of long SMPSs is not available. In this study, we developed laboratory and field experiments to evaluate three different SMPSs (SoilVUE10, Drill&Drop, and SMT500) in terms of measurement accuracy, sensor-to-sensor variability, and temperature stability. The laboratory experiment features a temperature-controlled lysimeter to evaluate intra-sensor variability and temperature stability of SMPSs. The field experiment features a water level-controlled sandbox and reference TDR measurements to evaluate the soil water measurement accuracy of the SMPS. In both experiments, a well-characterized fine sand was used as measurement medium to ensure homogeneous dielectric properties in the measurement domain of the sensors. The laboratory experiments with the lysimeter showed that the Drill&Drop sensor has the highest temperature sensitivity with a decrease of 0.014 m 3 m -3 per 10 °C, but at the same time showed the lowest intra- and inter-sensor variability. The field experiment with the sandbox showed that all three SMPSs have a similar performance (average RMSE ≈ 0.023 m 3 m -3 ) with higher uncertainties at intermediate soil moisture contents. The presented combination of laboratory and field tests were found to be well suited to evaluate the performance of SMPSs and will be used to test additional SMPSs in the future.

Background: Surgical site infections (SSI) present a substantial burden to patients and healthcare systems. This study aimed to elucidate the prevalence of SSIs in German hospitals and to quantify their clinical and economic burden based on German hospital reimbursement data (G-DRG)., Methods: This retrospective, cross-sectional study used a 2010-2016 G-DRG dataset to determine the prevalence of SSIs in hospital, using ICD-10-GM codes, after surgical procedures. The captured economic and clinical outcomes were used to quantify and compare resource use, reimbursement and clinical parameters for patients who had or did not have an SSI., Findings: Of the 4,830,083 patients from 79 hospitals, 221,113 were eligible. The overall SSI prevalence for the study period was 4.9%. After propensity-score matching, procedure type, immunosuppression and BMI ≥30 were found to significantly affect the risk of SSI (p<0.001). Mortality and length of stay (LOS) were significantly higher in patients who had an SSI (mortality: 9.3% compared with 4.5% [p<0.001]; LOS (median [interquartile range, IQR]): 28 [27] days compared with 12 [8] days [p<0.001]). Case costs were significantly higher for the SSI group (median [IQR]) €19,008 [25,162] compared with € 9,040 [7,376] [p<0.001]). A median underfunding of SSI was identified at €1,534 per patient., Interpretation: The dataset offers robust information about the "real-world" clinical and economic burden of SSI in hospitals in Germany. The significantly increased mortality of patients with SSI, and their underfunding, calls for a maximization of efforts to prevent SSI through the use of evidence-based SSI-reduction care bundles., Competing Interests: CE is a member of JnJ advisory boards. He received in the past three years honoraria for lecturing from Menarini, MSD and Pfizer. CM, KM and KMP are employees of Johnson & Johnson Medical GmbH MW is CEO and shareholder and WH employee of inspiring-health, which received funds from Johnson & Johnson Medical GmbH. The funding corporations did not affect the study design, analysis and manuscript writing; they were based only on authors decisions. DJL is a member of JnJ advisory panels and teaching groups., (Copyright: © 2022 Eckmann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Strategic management is becoming increasingly important for sustainable management in healthcare. The reasons for this can be seen in the increasing complexity, dynamics and uncertainty of the system's regimes and the resulting need for strategic thinking in a long-term period. The scientific discussion of this issue is the aim of the present analytical framework. The starting point is the definition of the term strategic management itself, followed by a reflection on the requirements resulting from the changes in the political, social and economic value systems of our post-industrial society. In this context, Dynaxity Zone III is used to explain the long-term perspective, the high levels of complexity and uncertainty and the responsibility of strategic management as important parameters. For a practical illustration, we demonstrate two selected applications (German hospital financing systems and development process of implants) and how the implementation of strategic management in the health care system shows success.

Insects behaviorally thermoregulate across the diel cycle, and their preferred microhabitats change based on current resources available and the thermal performance optima of traits. Specific combinations of traits being prioritized are set by life history strategies, making life history an important intrinsic determinant of thermal preferences. However, we do not know how life history strategies shape plasticity of behavioral thermoregulation, limiting our ability to predict responses to environmental variability. We compared female variable field crickets ( Gryllus lineaticeps ) that are flight-capable (long-winged) and flightless (short-winged) to test the hypothesis that life history strategy determines plasticity of thermal preferences across the diel cycle and following starvation. Thermal preferences were elevated during the nocturnal activity period, and long-winged crickets preferred warmer temperatures compared to short-winged crickets across the diel cycle when fully fed. However, thermal preferences of starved crickets were reduced compared to fed crickets. The reduction in thermal preferences was greater in long-winged crickets, resulting in similar thermal preferences between starved long- and short-winged individuals and reflecting a more plastic response. Thus, life history does determine plasticity in thermoregulatory behaviors following resource limitations and effects of life history on thermal preferences are context dependent., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Innovations are the source of all human development and improvement of quality of life. At the same time, they challenge existing standards, solutions and societal patterns. In health care in particular, innovations enable us to treat previously incurable diseases or to make better use of scarce resources. However, they also make existing health care technologies obsolete, force specialists to learn completely new methods and require high investments. Consequently, in this paper we develop a conceptual framework model for the development, adoption and diffusion of innovations in health care. We analyse barriers and promoters of innovations, in particular meta-stability, costs, innovative ability and leadership and apply the framework to three innovations: personalized medicine, digital health, and implants. We conclude that strategic innovation management in healthcare is a prerequisite of the rapid development and adoption of innovations and the improvement of quality of life of the (aging) population.

Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding of tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, and open source computational methods. Using DLP+, we have generated a resource of 51,926 single-cell genomes and matched cell images from diverse cell types including cell lines, xenografts, and diagnostic samples with limited material. From this resource we have defined variation in mitotic mis-segregation rates across tissue types and genotypes. Analysis of matched genomic and image measurements revealed correlations between cellular morphology and genome ploidy states. Aggregation of cells sharing copy number profiles allowed for calculation of single-nucleotide resolution clonal genotypes and inference of clonal phylogenies and avoided the limitations of bulk deconvolution. Finally, joint analysis over the above features defined clone-specific chromosomal aneuploidy in polyclonal populations., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

High-grade serous ovarian cancer (HGSC) exhibits extensive malignant clonal diversity with widespread but non-random patterns of disease dissemination. We investigated whether local immune microenvironment factors shape tumor progression properties at the interface of tumor-infiltrating lymphocytes (TILs) and cancer cells. Through multi-region study of 212 samples from 38 patients with whole-genome sequencing, immunohistochemistry, histologic image analysis, gene expression profiling, and T and B cell receptor sequencing, we identified three immunologic subtypes across samples and extensive within-patient diversity. Epithelial CD8+ TILs negatively associated with malignant diversity, reflecting immunological pruning of tumor clones inferred by neoantigen depletion, HLA I loss of heterozygosity, and spatial tracking between T cell and tumor clones. In addition, combinatorial prognostic effects of mutational processes and immune properties were observed, illuminating how specific genomic aberration types associate with immune response and impact survival. We conclude that within-patient spatial immune microenvironment variation shapes intraperitoneal malignant spread, provoking new evolutionary perspectives on HGSC clonal dispersion., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Lifespan in poikilothermic organisms, such as Caenorhabditis elegans, can be substantially increased simply by decreasing growth temperature. To gain insights into the mechanistic underpinnings of this effect, we investigated the effects of temperature in development and adulthood on C. elegans lifespan. We found that worms exposed to 25°C during development and shifted to 15°C in adulthood exhibited an even longer lifespan than animals constantly kept at 15°C. Analysis of the in vivo redox status demonstrated that at 25°C, C. elegans larvae have a more reduced redox state and higher Prdx-2 expression levels than animals raised at 15°C. Worms lacking prdx-2 fail to show the additional lifespan extension upon shift from 25°C to 15°C and reveal a lifespan similar to prdx-2 worms always kept at 15°C. These results suggest that transiently altering the in vivo redox state during development can have highly beneficial long-term consequences for organisms., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Infections and colonisations with multidrug-resistant organisms (MDROs) increasingly affect different types of healthcare facilities worldwide. So far, little is known about additional costs attributable to MDROs outside hospitals. The aim of this study was to analysis the economic burden of multidrug-resistant bacteria in nursing homes in Germany., Setting: The cost analysis is performed from a microeconomic perspective of the healthcare facilities. Study took place in six long-term care facilities in north-eastern Germany., Participants: Data of 71 residents with a positive MDRO status were included., Primary and Secondary Outcome Measures: The study analysed MDRO surveillance data from 2011 to 2013. It was supplemented by an empirical analysis to determine the burden on staff capacity and materials consumption., Results: 11,793 days with a positive multidrug-resistant pathogen diagnosis could be included in the analysis. On average, 11.8 (SD ± 6.3) MDRO cases occurred per nursing home. Mean duration per case was 163.3 days (SD ± 97.1). The annual MDRO-related costs varied in nursing homes between €2449.72 and €153,263.74 on an average €12,682.23 per case. Main cost drivers were staff capacity (€43.95 per day and €7177.04 per case) and isolation materials (€24.70 per day and €4033.51 per case)., Conclusions: The importance of MDROs in nursing homes could be confirmed. MDRO-related cost data in this specific healthcare sector were collected for the first time. Knowledge about the burden of MDROs will enable to assess the efficiency of hygiene intervention measures in nursing homes in the future., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Increased numbers of adherent invasive Escherichia coli (AIEC) have been found in Crohn's disease (CD) patients. In this report, we investigate the potential of the probiotic Escherichia coli Nissle 1917 (EcN) to reduce features associated with AIEC pathogenicity in an already established infection with AIEC reference strain LF82.

High levels of fatty acid synthase (FAS) expression have been reported in hormone receptor-positive tumors, including prostate, breast, and ovarian cancers, and its inhibition reduces tumor growth in vitro and in vivo. Similar to other hormone receptor-positive tumor types, meningiomas are progesterone receptor- and estrogen receptor-immunoreactive brain tumors. To define the role of FAS in human meningioma growth control, we first analyzed the FAS expression using a tissue microarray containing 38 meningiomas and showed increased FAS expression in 70% of atypical WHO grade II and anaplastic WHO grade III meningiomas compared with 10% of benign WHO grade I tumors. We next confirmed this finding by real-time PCR and Western blotting. Second, we demonstrated that treatment with the FAS inhibitor, cerulenin (Cer), significantly decreased meningioma cell survival in vitro. Third, we showed that Cer treatment reduced FAS expression by modulating Akt phosphorylation (activation). Fourth, we demonstrated that Cer treatment of mice bearing meningioma xenografts resulted in significantly reduced tumor volumes associated with increased meningioma cell death. Collectively, our data suggest that the increased FAS expression in human meningiomas represents a novel therapeutic target for the treatment of unresectable or malignant meningioma.

DNA samples from 339 Crohn's disease (CD) and 407 randomly selected controls from the Auckland (New Zealand) IBD project, were genotyped for five common single nucleotide polymorphisms in IL-23R (rs11805303, rs7517847, rs1343151, rs11209026, and rs10889677) and two in IL-12B (rs1363670 and rs6887695). While the IL-12B variants did not show an overall association and other IL23R variants led to minor changes in the risk of CD, rs1343151 and/or rs7517847 variants in the IL-23R gene strongly reduced the risk of developing CD at both allelic and genotype levels. A significantly decreased risk of first diagnosis of childhood CD was observed in individuals carrying the A allele of rs1343151, or between 17-40 y in individuals carrying the G allele in rs7517847 of IL-23R. A significantly decreased risk of ileocolonic or structuring disease was observed in individuals carrying the A allele in either rs11209026 or rs1343151, or the G allele in rs7517847 of IL-23R, and when such individuals did develop the disease, they were unlikely to require a bowel resection. Certain haplotypes very strongly modified risk. There was evidence for interactions of IL-23R variants with the NOD2 wild-type (d/d) genotype. Down-regulating the function of the IL-23R gene may decrease CD risk in the normal population.

Carrying a functional single nucleotide polymorphism (L503F, c. 1672 C>T) in the gene for the Na-dependent organic cation transporter (OCTN1), increases the risk of Crohn's disease (CD) in some, but not all, populations. Case-control data on New Zealand Caucasians show no differences for CD risk between individuals carrying the L503F OCTN1 C-allele when compared with those carrying the variant T-allele. However, more of the New Zealand CD cases report intolerance to maize and mushrooms than those who report beneficial effects or no differences. The OCTN1 gene encodes a transporter for ergothionine, a fungal metabolite at high levels in mushrooms but not widely common in other dietary items. An inability to tolerate mushrooms showed statistically significant associations with the variant OCTN1 genotype. That is, among those individuals reporting adverse effects from mushrooms, there was a higher frequency of the variant T-allele when compared with the general population, or with CD patients overall. We believe that this is a novel gene-diet association, suggesting that individuals carrying the OCTN1 variant single nucleotide polymorphism may have an enhanced risk of adverse symptoms associated with consuming mushrooms. Nutrigenomic approaches to dietary recommendations may be appropriate in this group.

Two closely related pathogenic species have evolved in the genus Neisseria: N. meningitidis and N. gonorrhoeae, which occupy different host niches and cause different clinical entities. In contrast to the pathogen N. gonorrhoeae, N. meningitidis is a commensal and only rarely becomes invasive. Little is known about the genetic background of the entirely different lifestyles in these closely related species. Meningococcal NMB1843 encodes a transcriptional regulator of the MarR family. The gonococcal homologue FarR regulates expression of farAB, mediating fatty acid resistance. We show that NmFarR also directly interacts with NmfarAB. Yet, by contrast to N. gonorrhoeae, no significant sensitivity to fatty acids was observed in a DeltafarR mutant due to intrinsic resistance of meningococci. Further analyses identified an NmFarR-repressed protein absent from N. gonorrhoeae. This protein is the meningococcus-specific adhesin and vaccine component NadA that has most likely been acquired by horizontal gene transfer. NmFarR binds to a 16 base pair palindromic repeat within the nadA promoter. De-repression of nadA resulted in significantly higher association of a DeltafarR strain with epithelial cells. Hence NmFarR has gained control over a meningococcus-specific gene involved in host colonization and thus contributed to divergent niche adaptation in pathogenic Neisseriae.

Background: The nucleotide-binding oligomerization domain containing 1 (NOD1) gene encodes a pattern recognition receptor that senses pathogens, leading to downstream responses characteristic of innate immunity. We investigated the role of NOD1 single nucleotide polymorphisms (SNPs) on IBD risk in a New Zealand Caucasian population, and studied Nod1 expression in response to bacterial invasion in the Caco2 cell line., Findings: DNA samples from 388 Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis patients and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common SNPs in NOD1, using the MassARRAY iPLEX Gold assay. Transcriptional activation of the protein produced by NOD1 (Nod1) was studied after infection of Caco2 cells with Escherichia coli LF82. Carrying the rs2075818 G allele decreased the risk of CD (OR = 0.66, 95% CI = 0.50-0.88, p < 0.002) but not UC. There was an increased frequency of the three SNP (rs2075818, rs2075822, rs2907748) haplotype, CTG (p = 0.004) and a decreased frequency of the GTG haplotype (p = 0.02).in CD. The rs2075822 CT or TT genotypes were at an increased frequency (genotype p value = 0.02), while the rs2907748 AA or AG genotypes showed decreased frequencies in UC (p = 0.04), but not in CD. Functional assays showed that Nod1 is produced 6 hours after bacterial invasion of the Caco2 cell line., Conclusion: The NOD1 gene is important in signalling invasion of colonic cells by pathogenic bacteria, indicative of its' key role in innate immunity. Carrying specific SNPs in this gene significantly modifies the risk of CD and/or UC in a New Zealand Caucasian population.

Inflammatory bowel diseases (IBDs) comprising Crohn disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions with polygenic susceptibility. Interactions between TNF-alpha and TNF-alpha receptor play a fundamental role in inflammatory response. This study investigates the role that selected single nucleotide polymorphisms (SNPs) and haplotypes in the TNF-alpha receptor (TNSFRSF1B) gene play in the risk of IBD in a New Zealand Caucasian population. DNA samples from 388 CD, 405 UC, 27 indeterminate colitis patients, and 293 randomly selected controls, from Canterbury, New Zealand were screened for 3 common SNPs in TNSFRSF1B: rs1061622 (c.676T > C), rs1061624 (c.*1663A > G), and rs3397 (c.*1690T > C), using TaqMan technologies. Carrying the rs1061624 variant decreased the risk of UC in the left colon (OR 0.73, 95% CI = 0.54-1.00) and of being a smoker at diagnosis (OR 0.62; 95% CI = 0.40-0.96). Carrying the rs3397 variant decreased the risk of penetrating CD (OR 0.62, 95% CI = 0.40-0.95). Three marker haplotype analyses revealed highly significant differences between CD patients and control subjects (chi(2) = 29.9, df = 7, P = .0001) and UC cases and controls (chi(2) = 46.3, df = 7, P < .0001). We conclude that carrying a 3-marker haplotype in the TNSFRSF1B gene may increase (e.g., haplotype of GGC was 2.9-fold more in the CD or UCpatients) or decrease (e.g., TGT was 0.47-fold less in UC patients) the risk of IBD in a New Zealand Caucasian population.

Aim: To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-alpha) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand population, in the context of international studies., Methods: DNA samples from 388 patients with Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis (IC) and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common polymorphisms in the TNF-alpha receptor: -238 G-->A, -308 G-->A and -857C-->T, using a Taqman assay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies., Results: Individuals carrying the -308 G/A allele had a significantly (OR = 1.91, c2 = 17.36, P < 0.0001) increased risk of pancolitis, and a 1.57-fold increased risk (OR = 1.57, c2 = 4.34, P = 0.037) of requiring a bowel resection in UC. Carrying the -857 C/T variant decreased the risk of ileocolonic CD (OR = 0.56, c2 = 4.32, P = 0.037), and the need for a bowel resection (OR = 0.59, c2 = 4.85, P = 0.028). The risk of UC was reduced in individuals who were smokers at diagnosis, (OR = 0.48, c2 = 4.86, P = 0.028)., Conclusion: TNF-alpha is a key cytokine known to play a role in inflammatory response, and the locus for the gene is found in the IBD3 region on chromosome 6p21, known to be associated with an increased risk for IBD. The -308 G/A SNP in the TNF-alpha promoter is functional, and may account in part for the increased UC risk associated with the IBD3 genomic region. The -857 C/T SNP may decrease IBD risk in certain groups. Pharmaco- or nutrigenomic approaches may be desirable for individuals with such affected genotypes.

Surface barriers for waste disposal sites should prevent waste water and gas emission into the environment. It is necessary to assess their proper operation by monitoring the water regime of the containment. A set of three new water content measuring devices has been developed that provide an economical solution for monitoring the moisture distribution and water dynamic. They will give an early warning service if the barrier system is at risk of being damaged. The cryo soil moisture sensor 'LUMBRICUS' is an in situ self-calibrating absolute water content measuring device. It measures moisture profiles at spot locations down to 2.5 m depth with an accuracy of better than 1.5% and a depth resolution of 0.03 m. The sensor inherently measures density changes and initial cracks of shrinking materials like clay minerals. The large area soil moisture sensor 'TAUPE' is a moisture sensitive electric cable network to be buried in the mineral barrier material of the cover. A report will be given with results and experiences on an exemplary installation at the Waste Disposal Facility Karlsruhe-West. 800 m2 of the barrier construction have been continuously monitored since December 1997. Volumetric water content differences of 1.5% have been detected and localised within 4 m. This device is already installed in two other waste disposal sites. A modified 'TAUPE' was constructed for the control of tunnels and river dams as well. Thin sheet moisture sensor 'FORMI' is specifically designed for moisture measurements in liners like bentonite, textile and plastic. Due to its flexibility it follows the curvature of the liner. The sensor measures independently from neighbouring materials and can be matched to a wide range of different thickness of the material. The sensors are patented in several countries.