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Objectives: The Self-Management Analysis in Chronic Conditions (SMACC) checklist was developed as a guidance tool to support the development, comparison and evaluation of self-management support programmes for persons with a chronic condition. The checklist was based on a previously performed concept analysis of self-management. The aim of this study was to validate its content using an international Delphi study and to deliver a final version., Design: A two-round Delphi study was conducted between October 2022 and January 2023. Using the researchers' networks, professionals with research or clinical expertise in self-management support and chronic conditions were recruited via online purposive snowball sampling. Participants were asked to score each item of the checklist (16 items total) on 3 content validity indicators: (1) clarity and comprehensibility, (2) relevance and importance and (3) degree of alignment with the overall goal of the checklist to promote adequate and comprehensive self-management support programmes. A consensus threshold of 75% agreement was used. The participants were also asked general questions about the checklist as a whole and were asked to provide feedback considering its refinement., Results: Fifty-four professionals with an average 14.5 years of experience participated in round 1, 48 with an average 12.5 years of experience participated in round 2. The majority of professionals were from Western Europe. For the majority of items consensus was reached after round 1. In round 2, 3 of the 4 remaining items reached consensus, 1 last item was retained based on highly recurring feedback., Conclusions: The SMACC checklist was considered a valid and comprehensive tool to aid the development, evaluation and comparison of self-management support programmes. It was acknowledged as a useful instrument to supplement existing frameworks and was seen as feasible to implement in both research and clinical settings. Further validation in the field, with input from patients and peer experts, will be valuable., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The primary objective was to describe the occupations people engaged in more frequently during lockdown than before the coronavirus disease 2019 pandemic as a function of generation. The secondary objectives were to (i) describe the levels of importance, performance, and satisfaction for these occupations and (ii) identify factors affecting the levels of importance, performance, and satisfaction., Method: We conducted an online, cross-sectional survey of young adults (YAs, aged 18-39), middle-aged adults (MAs, aged 40-59), and older adults (OAs, aged 60 or over)., Results: 2534 participants (YAs: 47%, MAs: 33%, and OAs: 20%) cited 4500 occupations. The occupations in which people most engaged were leisure occupations (67%), followed by productive occupations (31%) and then self-care (2%) occupations. YAs gave a median (interquartile range) importance score of 8 (6; 9) to leisure, 8 (7; 10) to productivity, and 8 (7; 10) to self-care. MAs gave a median importance score of 8 (6; 10) to leisure, 8 (7; 10) to productivity, and 8 (7; 10) to self-care. OAs gave a median importance score of 8 (7; 10) to leisure, 8 (7; 9) to productivity, and 9 (8; 10) to self-care. In a pre-/postlockdown comparison, the changes in performance scores among YAs were +5 (3; 6) for leisure, +4 (2; 5) for productivity, and +4 (3; 6) for self-care. Among MAs, these changes were, respectively, +4 (3; 6), +3 (2; 5), and +4.5 (3; 6). Among OAs, these changes were, respectively, +3 (1; 5) for leisure, +3 (2; 5) for productivity, and +2 (0; 4) for self-care. The changes in satisfaction scores among YAs were +3 (0; 5) for leisure, +3 (0; 5) for productivity, and +3 (1; 6) for self-care. Among MAs, these changes were, respectively, +3 (0; 5), +2 (0; 4), and +5 (0; 6). Among OAs, these changes were, respectively, +2 (0; 4), +2 (0; 4), and +2 (0; 4)., Conclusions: Lockdown led to stronger engagements in quiet leisure and alternative forms of socialization. Occupational therapists may have a role in helping community-dwelling people to balance and structure their new daily routine., Competing Interests: The authors declare that there are no conflicts of interest with regard to the present study., (Copyright © 2023 Cynthia Engels et al.)

Treatment concepts in oncology are becoming increasingly personalized and diverse. Successively, changes in standards of care mandate continuous monitoring of patient pathways and clinical outcomes based on large, representative real-world data. The German Cancer Consortium's (DKTK) Clinical Communication Platform (CCP) provides such opportunity. Connecting fourteen university hospital-based cancer centers, the CCP relies on a federated IT-infrastructure sourcing data from facility-based cancer registry units and biobanks. Federated analyses resulted in a cohort of 600,915 patients, out of which 232,991 were incident since 2013 and for which a comprehensive documentation is available. Next to demographic data (i.e., age at diagnosis: 2.0% 0-20 years, 8.3% 21-40 years, 30.9% 41-60 years, 50.1% 61-80 years, 8.8% 81+ years; and gender: 45.2% female, 54.7% male, 0.1% other) and diagnoses (five most frequent tumor origins: 22,523 prostate, 18,409 breast, 15,575 lung, 13,964 skin/malignant melanoma, 9005 brain), the cohort dataset contains information about therapeutic interventions and response assessments and is connected to 287,883 liquid and tissue biosamples. Focusing on diagnoses and therapy-sequences, showcase analyses of diagnosis-specific sub-cohorts (pancreas, larynx, kidney, thyroid gland) demonstrate the analytical opportunities offered by the cohort's data. Due to its data granularity and size, the cohort is a potential catalyst for translational cancer research. It provides rapid access to comprehensive patient groups and may improve the understanding of the clinical course of various (even rare) malignancies. Therefore, the cohort may serve as a decisions-making tool for clinical trial design and contributes to the evaluation of scientific findings under real-world conditions., (© 2023. The Author(s).)

Laparoscopic surgery has evolved as a key technique for cancer diagnosis and therapy. While characterization of the tissue perfusion is crucial in various procedures, such as partial nephrectomy, doing so by means of visual inspection remains highly challenging. We developed a laparoscopic real-time multispectral imaging system featuring a compact and lightweight multispectral camera and the possibility to complement the conventional surgical view of the patient with functional information at a video rate of 25 Hz. To enable contrast agent-free ischemia monitoring during laparoscopic partial nephrectomy, we phrase the problem of ischemia detection as an out-of-distribution detection problem that does not rely on data from any other patient and uses an ensemble of invertible neural networks at its core. An in-human trial demonstrates the feasibility of our approach and highlights the potential of spectral imaging combined with advanced deep learning-based analysis tools for fast, efficient, reliable, and safe functional laparoscopic imaging.

Background: The population is ageing, and psychiatric disorders are common in older people. Those are associated with worsened quality of life. Although the positive relationship between dog ownership and physical health has been documented, data on mental health are scarcer, especially in community-dwelling older adults., Objective: We sought to establish whether owning a dog was associated with a lower number of symptoms of psychological disorders in community-dwelling older adults., Methods: We conducted a systematic review of the literature published between January 2005 and December 2020. We analysed comparative studies of the level of insomnia and symptoms of depression and/or anxiety among community-dwelling dog owners aged 70 and over., Results: The search identified 191 articles, of which 117 full texts were assessed for eligibility. Five cross-sectional studies and one before-after with control group study (assessing a total of 25,138 older adults) were included. The mean (range) NOS score (five studies) was 6.8/9 (5-9) and the EPOC score (one study) was 2/8. The association between the presence of a dog and depressive symptoms did not appear to be significant. Regular contact with a dog was associated with fewer symptoms of anxiety. None of the studies specifically examined sleep disorders., Conclusions: Although the presence of a dog did not appear to be related to the level of depressive symptoms among community-dwelling older adults, there might be a beneficial relationship with anxiety. Further investigation is needed - especially with regard to the type of dog and the type of relationship with the dog., (© 2022 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Faced with an ageing population, carers are real allies and partners who are essential to the smooth running of the care of elderly patients. The objective of this study was to analyse their needs in oncogeriatrics, in order to verify the relevance of developing a serious game to support them. Although the need for better support for carers in oncogeriatrics was recognized, they especially value the need for human exchanges., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Biobanks ensure the long-term storage and accessibility of biospecimens and corresponding data sets. Thus, they form the foundation for many research projects which may contribute to improving medical care. With the establishment of the German Biobank Node and Alliance, expertise in biobanking is bundled and strengthened. An important component within this research infrastructure is the set-up of an information technology (IT) network for allowing feasibility requests across individual biobanks., Objective: We aim to describe relevant aspects that have shaped the journey to interconnect biobanks, to enhance their visibility within the research-community, to harmonize data, and to enable feasibility searches to support access to available data and biosamples., Methods: To achieve this task, we resorted to a wide variety of methods: we ran a requirement analysis, decided on the mode of operation for the federated team of IT-developers and on the development approach itself, took related national and international initiatives into account, and concluded with evaluations of the developed software artefacts and the operation of the entire chain of applications., Results: We drew an IT framework including all heterogeneous data aspects derived from our requirement analysis and developed a comprehensive IT infrastructure. The successful implementation benefited from a smooth interaction of a federated IT team distributed across all participating sites that was even able to manage a major technology change mid-project. Authentication and project management services from associated partners could be integrated and the graphic user interface for an intuitive search tool for biospecimens was designed iteratively. The developed code is open source to ensure sustainability and the local implementation is concluded and functioning. The evaluation of the components was positive., Conclusions: The entire project had given ample opportunity for challenges, predictable and unpredictable-from the mode of operation to changing some of the initial ideas. We learned our lessons concerning personnel, budget planning and technical as well as manual monitoring as well as some requirements arising only during the process of the project. Nevertheless, we can here report a success story of a network infrastructure, highly agile and much easier in local installation than initially anticipated., Competing Interests: The authors have declared that no competing interests exist.

In the field of oncology, a close integration of cancer research and patient care is indispensable. Although an exchange of data between health care providers and other institutions such as cancer registries has already been established in Germany, it does not take advantage of internationally coordinated health data standards. Translational cancer research would also benefit from such standards in the context of secondary data use. This paper employs use cases from the German Cancer Consortium (DKTK) to show how this gap can be closed using a harmonised FHIR-based data model, and how to apply it to an existing federated data platform.

Introduction: Self-care, leisure, and productivity are important occupational domains for older adults' quality of life, which might be affected by cancer and its treatment. A great number of publications about older adults focus on function or self-care, so we aimed to analyse how cancer and its treatments affect leisure and productivity. Secondary objectives were to identify whether particular clinical and/or sociodemographic factors were associated with occupational disruptions and to assess the impact of rehabilitation approaches on leisure and productivity in this population., Methods: A systematic review of the 2009-2019 literature performed on Medline, Embase, and the Cochrane Central Register of Controlled Trials., Results: 1471 publications were retrieved: 48 full texts were assessed; seven of these (four cross-sectional studies, two cohort studies, and a case report) were reviewed, including data on 16668 people (12649 healthy controls, 3918 cancer survivors, and 101 ill patients). Older adults with comorbidities and a low level of activity before cancer diagnosis may be more at risk of occupational disruptions. However, studies focused more on physical activity than leisure and productivity. Two studies mentioned occupational therapy. Discussion . As cancer can become a chronic disease, it appears important to also offer occupation-centred assessments and follow-up., Conclusion: An occupation-centred approach could be developed; its effectiveness must be assessed., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Cynthia Engels et al.)

Urology has always been closely linked to technological progress. In the last few decades, we have witnessed increasing implementation of various technologies and innovations in subdisciplines of urology. While conventional laparoscopy is increasingly being replaced by robot-assisted procedures and the introduction of new robotic systems from various manufactures will continue for years, the field of endourolgy is still not dominated by robotic systems. However, new systems (e.g., autonomous, robot-controlled aquablation of the prostate) are becoming increasingly popular and numerous development projects will also probably change clinical care in coming years. In addition, further advancements in the combination of robotics with intraoperative navigation through the integration of imaging and augmented-reality (AR) and virtual reality (VR) technology can be expected. This combination of navigation and robotic technology is already being used successfully in prostate biopsy.

Background: Although evidence-based practice (EBP) has been spreading since the 1990s, it has not yet been sufficiently implemented., Aim: Following the reform of initial training for healthcare professions in France 2012, we sought to determine whether the new curriculum was associated with more frequent use of EBP., Methods: We performed an online, cross-sectional survey of nurses, occupational therapists, and podiatrists (divided into pre- and post-reform groups) in June 2018. The questionnaire covered demographic data, use of EBP, and the perception of EBP. As holding a master's degree may enhance knowledge and use of EBP, we adjusted for this variable. Categories to analyze qualitative data were created regarding the five steps in EBP and its definition., Results: The total sample was N = 595 (pre-reform group n = 301; post-reform group n = 294). The proportion of respondents who frequently read the professional literature was lower in the post-reform group than in the pre-reform group (33% vs. 54%, respectively; OR [95% CI] = .52 [.37-.73]; p < .001). The main stated reasons for reading the professional literature were "keeping up to date with practice" and "making clinical decisions." Respondents in both groups mentioned a lack of time as the most frequent barrier to reading the literature (82%), a lack of access to bibliographical resources, and that EBP was not encouraged. Most professionals limited their definition of EBP to reading the literature and implementing research results., Linking Evidence to Action: There is a need to teach the five steps of EBP more explicitly and to embed its position into daily practice, for example, through reflective analysis practice. Professional trainings about EBP should be offered on a regular basis. Guidance coming from the healthcare directorate should include expected daily practice time for reading and journal club and giving more access to international healthcare literature., (© 2020 Sigma Theta Tau International.)

Earth is home to over 350,000 vascular plant species that differ in their traits in innumerable ways. A key challenge is to predict how natural or anthropogenically driven changes in the identity, abundance and diversity of co-occurring plant species drive important ecosystem-level properties such as biomass production or carbon storage. Here, we analyse the extent to which 42 different ecosystem properties can be predicted by 41 plant traits in 78 experimentally manipulated grassland plots over 10 years. Despite the unprecedented number of traits analysed, the average percentage of variation in ecosystem properties jointly explained was only moderate (32.6%) within individual years, and even much lower (12.7%) across years. Most other studies linking ecosystem properties to plant traits analysed no more than six traits and, when including only six traits in our analysis, the average percentage of variation explained in across-year levels of ecosystem properties dropped to 4.8%. Furthermore, we found on average only 12.2% overlap in significant predictors among ecosystem properties, indicating that a small set of key traits able to explain multiple ecosystem properties does not exist. Our results therefore suggest that there are specific limits to the extent to which traits per se can predict the long-term functional consequences of biodiversity change, so that data on additional drivers, such as interacting abiotic factors, may be required to improve predictions of ecosystem property levels.

Conceiving healthcare research as approachable by anyone makes it a tool for knowledge construction. The objective is to learn and to conduct a meaningful work, in order to improve quality of care. Research-as knowledge-forces reconsideration, deconstruction before reconstruction. To stay informed, to learn and to develop a research does not only imply to know what and where to search, but also to read in English, in one's field of practice. Teamwork allows to do with others what might be difficult alone., (Copyright © 2020. Publié par Elsevier Masson SAS.)

Background: In some European countries, including France, older patients with functional decline in acute units are transferred to geriatric rehabilitation units. Some patients may not benefit from their stay in a geriatric rehabilitation unit and paradoxically worsened their functional status. Previous prognostic models of functional decline are based on only baseline parameters. However, some events can occur during rehabilitation and modify the association between baseline parameters and rehabilitation performance such as heart failure episode, falls or hospital-acquired infection (HAI). The incidence of functional decline in these units and factors associated with this decline have not been clearly identified., Methods: We used a prospective cohort of consecutive patients aged ≥75 years admitted to a geriatric rehabilitation unit in a French university hospital. The main endpoint was functional decline defined by at least an one-point decrease in Activities of Daily Living (ADL) score during the stay. Baseline social and geriatric characteristics were recorded and comorbidities were sought by the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). During follow-up, hospital-acquired infection (HAI) was recorded, as was ADL score at discharge. Multivariate logistic regression and mediation analyses were used to identify factors associated with ADL decrease., Results: Among the 252 eligible patients, 160 (median age 84 years [interquartile range (IQR) 80-88] had available ADL scores at baseline (median score 7 [IQR 4-10]) and at discharge (median 9 [6-12]). Median CIRS-G score was 11 [8-13], 23 (14%) had a pulmonary HAI; 28 (17.5%) showed functional decline. On multivariable analysis, functional decline was associated with comorbidities (global CIRS-G score, P = 0.02, CIRS-G for respiratory disease [CIRS-G-R] ≥2, P = 0.02, or psychiatric disease, P = 0.02) and albumin level < 35 g/l (p = 0.03). Significant associations were found between functional decline and CIRS-G-R (OR 3.07 [95%CI 1.27-7.41], p = 0.01), between functional decline and pulmonary HAI (OR 3.12 [1.17-8.32],p = 0.02), and between CIRS-G-R and pulmonary HAI (OR 12.9[4.4-37.7], p = 0.0001). Theses associations and the reduced effect of CIRS-G-R on functional decline after adjusting for pulmonary HAI (OR 2.26 [0.83-6.16], p = 0.11) suggested partial mediation of pulmonary HAI in the relation between CIRS-G-R and functional decline., Conclusion: Baseline comorbidities were independently associated with functional decline in patients hospitalized in a geriatric rehabilitation unit. Pulmonary HAI may have mediated this association. We need to better identify patients at risk of functional decline before transfer to a rehabilitation unit and to test the implementation of modern and individual programs of rehabilitation outside the hospital for these patients.

The increasing networking of data systems in medicine is not only leading to modern interdisciplinarity in the sense of cooperation between different medical departments, but also poses new challenges regarding the building and room infrastructure. The surgical operating room of the future expands or augments its reality, away from the pure building characteristics, towards an intelligent and communicative space platform. The building infrastructure (operating theatre) serves as sensor and actuator. Thus, it is possible to inform about missing diagnostics as well as to register them directly in the contextualization of the planned surgical intervention or to integrate them into the processes. Integrated operating theatres represent a comprehensive computer platform based on a corresponding system architecture with software-based protocols. An underlying modular system consisting of various modules for image acquisition and analysis, interaction and visualization supports the integration and merging of heterogeneous data that are generated in a hospital operation. Integral building data (e.g., air conditioning, lighting control, device registration) are merged with patient-related data (age, type of illness, concomitant diseases, existing diagnostic CT and MRI images). New systems coming onto the market, as well as already existing systems will have to be measured by the extent to which they will be able to guarantee this integration of information-similar to the development from mobile phone to smartphone. Cost reduction should not be the only legitimizing argument for the market launch, but the vision of a new quality of surgical perception and action.

Purpose: Live intra-operative functional imaging has multiple potential clinical applications, such as localization of ischemia, assessment of organ transplantation success and perfusion monitoring. Recent research has shown that live monitoring of functional tissue properties, such as tissue oxygenation and blood volume fraction, is possible using multispectral imaging in laparoscopic surgery. While the illuminant spectrum is typically kept constant in laparoscopic surgery and can thus be estimated from preoperative calibration images, a key challenge in open surgery originates from the dynamic changes of lighting conditions., Methods: The present paper addresses this challenge with a novel approach to light source calibration based on specular highlight analysis. It involves the acquisition of low-exposure time images serving as a basis for recovering the illuminant spectrum from pixels that contain a dominant specular reflectance component., Results: Comprehensive in silico and in vivo experiments with a range of different light sources demonstrate that our approach enables an accurate and robust recovery of the illuminant spectrum in the field of view of the camera, which results in reduced errors with respect to the estimation of functional tissue properties. Our approach further outperforms state-of-the-art methods proposed in the field of computer vision., Conclusion: Our results suggest that low-exposure multispectral images are well suited for light source calibration via specular highlight analysis. This work thus provides an important first step toward live functional imaging in open surgery.

Background: Understanding how professional competencies are actually enacted in clinical practice can help university programs better prepare their graduates. The study aimed to describe 1) the perceived competency level of occupational therapists holding an entry-to-practice master's degree 2) the factors perceived as impacting the enactment of competencies; and 3) the strategies used to maintain and further develop level of competency in the seven practice roles: expert in enabling occupation, communicator, collaborator, practice manager, change agent, scholarly practitioner and professional., Methods: Descriptive two-phase mixed methods sequential design. The quantitative phase consisted of an online survey sent to all occupational therapists holding an entry-to-practice master's degree in Quebec, Canada (n = 1196), followed by focus group discussions with a subset of participants. Analysis used descriptive statistics and the Framework Approach for content analysis of focus group data. Competencies were theoretically anchored into the Profile of Occupational Therapist Practice in Canada (an equivalent to CanMEDS framework) and we used the Theoretical Domain Framework to collect and describe perceived factors and strategies., Results: Response rate to Phase 1 was 26.5% (n = 317/1196). The communicator, collaborator and professional roles were perceived as highly solicited in practice, valued and were rated more frequently at a higher competency level as compared to the other four roles (expert, manager, change agent and scholar roles). Focus group participants (n = 16) mentioned that both individual and organisational factors influence enactment of competencies. Consulting colleagues was the preferred strategy to support the scholar role, often described as foundational for the development of expertise., Conclusion: This descriptive study provides valuable information as to how the seven roles are enacted in practice. Though the scholar role is highly valued by clinicians and organizations, insufficient time is allotted to searching for evidence and reflection in practice. Strategies emerging from the results are mainly directed toward this role with an emphasis on using of peers as a source of evidence. Future studies could explore how contextual factors influence the enactment of competencies across different professions as well as how these evolve over time.

Introduction: The Minimum Information About BIobank data Sharing (MIABIS) was initiated in 2012. MIABIS aims to create a common biobank terminology to facilitate data sharing in biobanks and sample collections. The MIABIS Core terminology consists of three components describing biobanks, sample collections, and studies, in which information on samples and sample donors is provided at aggregated form. However, there is also a need to describe samples and sample donors at an individual level to allow more elaborate queries on available biobank samples and data. Therefore the MIABIS terminology has now been extended with components describing samples and sample donors at an individual level. Materials and Methods: The components were defined according to specific scope and use cases by a large group of experts, and through several cycles of reviews, according to the new MIABIS governance model of BBMRI-ERIC (Biobanking and Biomolecular Resources Research Infrastructure-European Research Infrastructure Consortium). The guiding principles applied in developing these components included the following terms: model should consider only samples of human origin, model should be applicable to all types of samples and all sample donors, and model should describe the current status of samples stored in a given biobank. Results: A minimal set of standard attributes for defining samples and sample donors is presented here. We added an "event" component to describe attributes that are not directly describing samples or sample donors but are tightly related to them. To better utilize the generic data model, we suggest a procedure by which interoperability can be promoted, using specific MIABIS profiles. Discussion: The MIABIS sample and donor component extensions and the new generic data model complement the existing MIABIS Core 2.0 components, and substantially increase the potential usability of this terminology for better describing biobank samples and sample donors. They also support the use of individual level data about samples and sample donors to obtain accurate and detailed biobank availability queries.

Sub-optimal nitrogen (N) conditions reduce maize yield due to a decrease in two sink components: kernel set and potential kernel weight. Both components are established during the lag phase, suggesting that they could compete for resources during this critical period. However, whether this competition occurs or whether different genotypic strategies exist to optimize photoassimilate use during the lag phase is not clear and requires further investigation. We have addressed this knowledge gap by conducting a nutrient solution culture experiment that allows abrupt changes in N level and light intensity during the lag phase. We investigated plant growth, dry matter partitioning, non-structural carbohydrate concentration, N concentration, and 15 N distribution (applied 4 days before silking) in plant organs at the beginning and the end of the lag phase in two maize hybrids that differ in grain yield under N-limited conditions: one is a nitrogen-use-efficient (EFFI) genotype and the other is a control (GREEN) genotype that does not display high N use efficiency. We found that the two genotypes used different mechanisms to regulate kernel set. The GREEN genotype showed a reduction in kernel set associated with reduced dry matter allocation to the ear during the lag phase, indicating that the reduced kernel set under N-limited conditions was related to sink restrictions. This idea was supported by a negative correlation between kernel set and sucrose/total sugar ratios in the kernels, indicating that the capacity for sucrose cleavage might be a key factor defining kernel set in the GREEN genotype. By contrast, the kernel set of the EFFI genotype was not correlated with dry matter allocation to the ear or to a higher capacity for sucrose cleavage; rather, it showed a relationship with the different EFFI ear morphology with bigger kernels at the apex of the ear than in the GREEN genotype. The potential kernel weight was independent of carbohydrate availability but was related to the N flux per kernel in both genotypes. In conclusion, kernel set and potential kernel weight are regulated independently, suggesting the possibility of simultaneously increasing both sink components in maize., (Copyright © 2020 Paponov, Paponov, Sambo and Engels.)

Purpose: Tumor-infiltrating lymphocytes (TILs) are associated with pathological complete response (pCR) and survival after neoadjuvant chemotherapy (NAC) in patients with early breast cancer. We investigated the prognostic and predictive role of TILs, macrophages, and HLA class 1 expression after NAC with or without the potentially immune modulating compound zoledronic acid (ZA)., Methods: Baseline tumor biopsies from 196 patients in the NEOZOTAC trial were analyzed for CD8 (cytotoxic T-cells), FoxP3 (regulatory T-cells), CD68 (macrophages), and HLA class I (HCA2/HC10) expression by immunohistochemistry and subsequently related to pCR and disease-free survival (DFS)., Results: A strong intratumoral CD8+ infiltration or expression of HLA class 1 by cancer cells was associated with a higher pCR rate (p < 0.05). Clinical benefit of high CD8+ T-cell infiltration was found when cancer cells expressed HLA class 1 (pCR: 21.8% vs. 6.7%, p = 0.04) but not when HLA class 1 expression was lost or downregulated (pCR: 5.9% vs. 0%, p = 0.38). Interaction analyses revealed survival benefit between HLA class 1 expression and strong CD8+ T-cell infiltration, whereas in the absence or downregulation of HLA class 1 expression, high levels of CD8+ T-cells were associated with survival disadvantage (p for interaction 0.01; hazard ratio 0.41, 95% CI 0.15-1.10, p = 0.08 and hazard ratio 7.67, 95% CI 0.88-66.4, p = 0.07, respectively). Baseline immune markers were not related to ZA treatment., Conclusions: Strong baseline tumor infiltration with CD8+ T-cells in the presence of tumoral HLA class 1 expression in patients with HER2-negative breast cancer is related to a higher pCR rate and a better DFS after NAC.

Objectives: Healthcare professionals are expected to firmly ground their practice in sound evidence. That implies that they know and use evidence-based medicine (EBM). In this study, our aim was to know how often health professionals actually made use of EBM in their daily practice., Design: A questionnaire survey of healthcare professionals., Participants: Healthcare professionals who attended six university postgraduate courses. 226 answered the questionnaire (144 physicians, 64 nurses and 24 pharmacists; response rate 63.3%)., Setting: 56.5% of respondents worked in hospitals (mostly non-teaching), 25.0% in nursing homes and 10.2% in primary care. All participants were French-speaking and lived in France or Switzerland., Measures: Declared degree of knowledge and use of EBM, use of EBM-related information sources., Results: Overall, 14.2% of respondents declared to use EBM regularly in their daily practice and 15.6% declared to use EBM only occasionally. The remaining respondents declared they: knew about EBM but did not use it (33.1%), had just heard about EBM (31.9%) or did not know what EBM is (4.0%). Concerning the use of EBM-related information sources, 83.4% declared to use at least monthly (or more often) clinical guidelines, 47.1% PubMed, 21.3% the Cochrane Library and 6.4% other medical databases.Fewer pharmacists (12%) declared to use EBM in their practice than nurses (22%) or doctors (36%). No difference appeared when analysed by gender, work setting or years after graduation. The most frequent obstacles perceived for the practice of EBM were: lack of general knowledge about EBM, lack of skills for critical appraisal and lack of time., Conclusions: Only a minority of health professionals-with differences between physicians, nurses and pharmacists-declare to regularly use EBM in their professional practice. A larger proportion appears to be interested in EBM but seems to be deterred by their lack of knowledge, skills and personal time., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Complex interactions occur between cancer cells and cells in the tumor microenvironment. In this study, the prognostic value of the interplay between tumor-stroma ratio (TSR) and the immune status of tumors in breast cancer patients was evaluated., Methods: A cohort of 574 breast cancer patients was analyzed. The percentage of tumor stroma was visually estimated on Hematoxylin and Eosin (H&E) stained histological tumor tissue sections. Immunohistochemical staining was performed for classical human leukocyte antigen (HLA) class I, HLA-E, HLA-G, markers for regulatory T (Treg) cells, natural killer (NK) cells and cytotoxic T-lymphocytes (CTLs)., Results: TSR (P < .001) and immune status of tumors (P < .001) were both statistically significant for recurrence free period (RFP) and both independent prognosticators (P < .001) in which tumors with a high stromal content behave more aggressively as well as tumors with a low immune status. Ten years RFP for patients with a stroma-low tumor and high immune status profile was 87% compared to 17% of patients with a stroma-high tumor combined with low immune status profile (P < .001). Classical HLA class I is the most prominent immune marker in the immune status profiles., Conclusions: Determination of TSR is a simple, fast and cheap method. The effect on RFP of TSR when combined with immune status of tumors or expression of classical HLA class I is even stronger. Both are promising for further prediction and achievement of tailored treatment for breast cancer patients.

Biodiversity ensures ecosystem functioning and provisioning of ecosystem services, but it remains unclear how biodiversity-ecosystem multifunctionality relationships depend on the identity and number of functions considered. Here, we demonstrate that ecosystem multifunctionality, based on 82 indicator variables of ecosystem functions in a grassland biodiversity experiment, increases strongly with increasing biodiversity. Analysing subsets of functions showed that the effects of biodiversity on multifunctionality were stronger when more functions were included and that the strength of the biodiversity effects depended on the identity of the functions included. Limits to multifunctionality arose from negative correlations among functions and functions that were not correlated with biodiversity. Our findings underline that the management of ecosystems for the protection of biodiversity cannot be replaced by managing for particular ecosystem functions or services and emphasize the need for specific management to protect biodiversity. More plant species from the experimental pool of 60 species contributed to functioning when more functions were considered. An individual contribution to multifunctionality could be demonstrated for only a fraction of the species.

Generation Y’s (born between 1981 and 1999) educational approach in healthcare studies raises questions about their expectations and which teaching methods to use with this generation. The study involved third year students of occupational therapy. One hundred and twelve students were consulted in September 2012 and September 2013 about their expectations regarding the courses and the teaching methods which were offered. Results allowed to highlight firstly the importance of the usefulness of the course and secondly expectations regarding the teachers’ soft skills. If the link between soft skills and success was pointed out in many studies, only a few studies focus on the teachers’ own soft skills development in order to respond to students’ expectations in higher education. This is the topic of this article, which main interest could be the means to develop teaching methods adapted to this students’ generation.

Spider plant is among the important indigenous African leafy vegetables having the potential to contribute to food and nutritional security in sub-Saharan Africa. The main objective of this study was to quantify the mineral concentration, to identify and quantify glucosinolates and flavonoids in spider plant and further to characterize spider plant entries using important morphological traits. Thirty spider plant entries from different African countries, comprising of farmers' cultivars, gene bank accessions and advanced lines were grown in a field experiment and harvested for leaves, stems, flowers and siliques at different developmental stages. Five plant types based on the stem and petiole colorations were identified. Significant genotypic differences were shown for all the morphological traits except for 100 seed weight and silique weight. High mineral concentrations in the leaf tissue were observed especially for potassium, calcium, magnesium, phosphorus, iron, manganese and zinc. The aliphatic 3-hydroxypropyl glucosinolate was the main glucosinolate detected in all tissues with the highest concentrations in the reproductive organs. Glycosides of quercetin, kaempferol and isorhamnetin were the main flavonoids. Isorhamnetin glycosides were detected in trace amounts in both, leaves and inflorescences, while quercetin and kaempferol glycosides were the dominant flavonoids in the leaves and inflorescences, respectively. This knowledge of beneficial nutrient contents is an incentive for promoting spider plant consumption for improved human health while the morphological diversity analysis will be important for the further development of the spider plant germplasm., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The diverse community of microbes present in the human gut has emerged as an important factor for cancer risk, potentially by altering exposure to chemical carcinogens. In the present study, human gut bacteria were tested for their capacity to transform the carcinogenic heterocyclic amine 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx). Eubacterium hallii, Lactobacillus reuteri, and Lactobacillus rossiae were able to convert MelQx to a new microbial metabolite characterized on the basis of high-resolution mass spectrometry and NMR as 9-hydroxyl-2,7-dimethyl-7,9,10,11-tetrahydropyrimido[2',1':2,3]imidazo[4,5-f]quinoxaline (MelQx-M1), resulting from conjugation with activated glycerol. Acrolein derived from the decomposition of 3-hydroxypropionaldehyde, which is the product of bacterial glycerol/diol dehydratase activity, was identified as the active compound responsible for the formation of MelQx-M1. A complex human gut microbial community obtained from invitro continuous intestinal fermentation was found to also transform MelQx to MelQx-M1. MelQx-M1 had slightly reduced cytotoxic potency toward human colon epithelial cells invitro, and diminished mutagenic potential toward bacteria after metabolic activation. As bacterially derived acrolein also transformed 2 other HCAs, namely 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3-methylimidazo[4,5-f]quinoline, these results generalize the capacity of gut microbiota to detoxify HCAs in the gut, potentially modulating cancer risk., (© The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology.)

Glycerol/diol dehydratases catalyze the conversion of glycerol to 3-hydroxypropionaldehyde (3-HPA), the basis of a multi-component system called reuterin. Reuterin has antimicrobial properties and undergoes chemical conjugation with dietary heterocyclic amines (HCAs). In aqueous solution reuterin is in dynamic equilibrium with the toxicant acrolein. It was the aim of this study to investigate the extent of acrolein formation at various physiological conditions and to determine its role in biological and chemical activities. The application of a combined novel analytical approach including IC-PAD, LC-MS and NMR together with specific acrolein scavengers suggested for the first time that acrolein, and not 3-HPA, is the active compound responsible for HCA conjugation and antimicrobial activity attributed to reuterin. As formation of the HCA conjugate was observed in vivo, our results imply that acrolein is formed in the human gut with implications on detoxification of HCAs. We propose to re-define the term reuterin to include acrolein.

Eubacterium hallii is considered an important microbe in regard to intestinal metabolic balance due to its ability to utilize glucose and the fermentation intermediates acetate and lactate, to form butyrate and hydrogen. Recently, we observed that E. hallii is capable of metabolizing glycerol to 3-hydroxypropionaldehyde (3-HPA, reuterin) with reported antimicrobial properties. The key enzyme for glycerol to 3-HPA conversion is the cobalamin-dependent glycerol/diol dehydratase PduCDE which also utilizes 1,2-propanediol (1,2-PD) to form propionate. Therefore our primary goal was to investigate glycerol to 3-HPA metabolism and 1,2-PD utilization by E. hallii along with its ability to produce cobalamin. We also investigated the relative abundance of E. hallii in stool of adults using 16S rRNA and pduCDE based gene screening to determine the contribution of E. hallii to intestinal propionate formation. We found that E. hallii utilizes glycerol to produce up to 9 mM 3-HPA but did not further metabolize 3-HPA to 1,3-propanediol. Utilization of 1,2-PD in the presence and absence of glucose led to the formation of propanal, propanol and propionate. E. hallii formed cobalamin and was detected in stool of 74% of adults using 16S rRNA gene as marker gene (n = 325). Relative abundance of the E. hallii 16S rRNA gene ranged from 0 to 0.59% with a mean relative abundance of 0.044%. E. hallii PduCDE was detected in 63 to 81% of the metagenomes depending on which subunit was investigated beside other taxons such as Ruminococcus obeum, R. gnavus, Flavonifractor plautii, Intestinimonas butyriciproducens, and Veillonella spp. In conclusion, we identified E. hallii as a common gut microbe with the ability to convert glycerol to 3-HPA, a step that requires the production of cobalamin, and to utilize 1,2-PD to form propionate. Our results along with its ability to use a broad range of substrates point at E. hallii as a key species within the intestinal trophic chain with the potential to highly impact the metabolic balance as well as the gut microbiota/host homeostasis by the formation of different short chain fatty acids.

2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) is the most abundant food-derived heterocyclic aromatic amine in well-cooked meats and may contribute to the recognized carcinogenicity of processed meats. In this study, a panel of human gut microbes was tested for their ability to convert PhIP to a conjugate PhIP-M1. Eubacterium hallii was newly identified to catalyse the conversion of PhIP to PhIP-M1 with high efficiency. The reaction was shown to involve the metabolism of glycerol to 3-hydroxypropionaldehyde as a key pathway. The proficiency of E. hallii in transforming PhIP in the presence of a complex intestinal microbiota was confirmed using batch fermentations inoculated with effluents from a continuous intestinal fermentation model mimicking human proximal and distal colon microbiota. In batch fermentations inoculated with proximal colon microbiota, PhIP-M1 transformation corresponded to an up to 300-fold increase of E. hallii. In contrast, PhIP transformation of distal colon microbiota was low but increased by 120-fold after supplementation with E. hallii. These findings indicate for the first time the relevance of the abundant commensal strict anaerobe E. hallii in the transformation of a dietary carcinogen that could contribute to its detoxification in the human colon., (© 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Background: Predicting breast cancer outcome in older patients is challenging, as it has been shown that the available tools are not accurate in older patients. The PREDICT tool may serve as an alternative tool, as it was developed in a cohort that included almost 1800 women aged 65 years or over. The aim of this study was to assess the validity of the online PREDICT tool in a population-based cohort of unselected older patients with breast cancer., Methods: Patients were included from the population-based FOCUS-cohort. Observed 5- and 10-year overall survival were estimated using the Kaplan-Meier method, and compared with predicted outcomes. Calibration was tested by composing calibration plots and Poisson Regression. Discriminatory accuracy was assessed by composing receiver-operator-curves and corresponding c-indices., Results: In all 2012 included patients, observed and predicted overall survival differed by 1.7%, 95% confidence interval (CI)=-0.3-3.7, for 5-year overall survival, and 4.5%, 95% CI=2.3-6.6, for 10-year overall survival. Poisson regression showed that 5-year overall survival did not significantly differ from the ideal line (standardised mortality ratio (SMR)=1.07, 95% CI=0.98-1.16, P=0.133), but 10-year overall survival was significantly different from the perfect calibration (SMR=1.12, 95% CI=1.05-1.20, P=0.0004). The c-index for 5-year overall survival was 0.73, 95% CI=0.70-0.75, and 0.74, 95% CI=0.72-0.76, for 10-year overall survival., Conclusions: PREDICT can accurately predict 5-year overall survival in older patients with breast cancer. Ten-year predicted overall survival was, however, slightly overestimated.

Background: Procoagulant full-length tissue factor (flTF) and its minimally coagulant alternatively spliced isoform (asTF), promote breast cancer (BrCa) progression via different mechanisms. We previously showed that flTF and asTF are expressed by BrCa cells, resulting in autoregulation in a cancer milieu. BrCa cells often express hormone receptors such as the estrogen receptor (ER), leading to the formation of hormone-regulated cell populations., Objective: To investigate whether TF isoform-specific and ER-dependent pathways interact in BrCa., Methods: Tissue factor isoform-regulated gene sets were assessed using ingenuity pathway analysis. Tissues from a cohort of BrCa patients were divided into ER-positive and ER-negative groups. Associations between TF isoform levels and tumor characteristics were analyzed in these groups. BrCa cells expressing TF isoforms were assessed for proliferation, migration and in vivo growth in the presence or absence of estradiol., Results: Ingenuity pathway analysis pointed to similarities between ER- and TF-induced gene expression profiles. In BrCa tissue specimens, asTF expression was associated with grade and stage in ER-positive but not in ER-negative tumors. flTF was only associated with grade in ER-positive tumors. In MCF-7 cells, asTF accelerated proliferation in the presence of estradiol in a β1 integrin-dependent manner. No synergy between asTF and the ER pathway was observed in a migration assay. Estradiol accelerated the growth of asTF-expressing tumors but not control tumors in vivo in an orthotopic setting., Conclusion: Tissue factor isoform and estrogen signaling share downstream targets in BrCa; the concomitant presence of asTF and estrogen signaling is required to promote BrCa cell proliferation., (© 2015 International Society on Thrombosis and Haemostasis.)

Plant diversity strongly influences ecosystem functions and services, such as soil carbon storage. However, the mechanisms underlying the positive plant diversity effects on soil carbon storage are poorly understood. We explored this relationship using long-term data from a grassland biodiversity experiment (The Jena Experiment) and radiocarbon ((14)C) modelling. Here we show that higher plant diversity increases rhizosphere carbon inputs into the microbial community resulting in both increased microbial activity and carbon storage. Increases in soil carbon were related to the enhanced accumulation of recently fixed carbon in high-diversity plots, while plant diversity had less pronounced effects on the decomposition rate of existing carbon. The present study shows that elevated carbon storage at high plant diversity is a direct function of the soil microbial community, indicating that the increase in carbon storage is mainly limited by the integration of new carbon into soil and less by the decomposition of existing soil carbon.

Identification of patients who are at increased risk for contralateral breast cancer is essential to determine which patients should be routinely screened for contralateral breast cancer using MRI. The aim of this study was to assess the association of age and tumor morphology with contralateral breast cancer incidence in a large, nationwide population-based study in the Netherlands. All patients with breast cancer stage I-III, diagnosed between 1989 and 2009, were selected from the Netherlands Cancer Registry. The association between contralateral breast cancer risk with tumor morphology and age was assessed using competing-risk regression according to Fine & Gray. Overall, 194,898 patients were included. In multivariable analyses, lobular tumors were significantly associated with an increased risk of contralateral breast cancer within 6 months (cumulative incidence 1.9 %, subdistribution hazard ratio (SHR) 1.17, 95 % confidence interval (CI) 1.06-1.30 compared with 1.3 % in ductal tumors, p = 0.002). Age was also associated with an increased risk of contralateral breast cancer within 6 months (SHR 2.34, 95 % CI 2.08-2.62, p < 0.002 for patients over the age of 75 as compared to patients younger than 50 years). The absolute risk of contralateral breast cancer within 6 months is only slightly increased in patients with a lobular tumor and older patients. In our view, this small increased risk does not justify standard use of preoperative MRI based on tumor morphology or age alone. We propose a more personalized strategy in which additional risk factors (family history, prognosis of primary tumor, and others) may play a role.

Evidence exists for an immunomodulatory effect of endocrine therapy in hormone receptor-positive (HR+ve) breast cancer (BC). Therefore, the aim of this study was to define the prognostic and predictive value of tumor immune markers and the tumor immune profile in HR+ve BC, treated with different endocrine treatment regimens. 2,596 Dutch TEAM patients were treated with 5 years of adjuvant hormonal treatment, randomly assigned to different regimens: 5 years of exemestane or sequential treatment (2.5 years of tamoxifen-2.5 years of exemestane). Immunohistochemistry was performed for HLA class I, HLA-E, HLA-G, and FoxP3. Tumor immune subtypes (IS) (low, intermediate & high immune susceptible) were determined by the effect size of mono-immune markers on relapse rate. Patients on sequential treatment with high level of tumor-infiltrating FoxP3+ cells had significant (p = 0.019, HR 0.729, 95% CI 0.560-0.949) better OS. Significant interaction for endocrine treatment and FoxP3+ presence was seen (OS p < 0.001). Tumor IS were only of prognostic value for the sequentially endocrine-treated patients (RFP: p = 0.035, HR intermediate IS 1.420, 95% CI 0.878-2.297; HR low IS 1.657, 95% CI 1.131-2.428; BCSS: p = 0.002, HR intermediate IS 2.486, 95% CI 1.375-4.495; HR low IS 2.422, 95% CI 1.439-4.076; and OS: p = 0.005, HR intermediate IS 1.509, 95% CI 0.950-2.395; HR low IS 1.848, 95% CI 1.277-2.675). Tregs and the tumor IS presented in this study harbor prognostic value for sequentially endocrine-treated HR+ve postmenopausal BC patients, but not for solely exemestane-treated patients. Therefore, these markers could be used as a clinical risk stratification tool to guide adjuvant treatment in this BC population.

In December 2008, the US Food and Drug Administration (FDA) issued a guidance for industry requiring sponsors to demonstrate that a new antidiabetic therapy being developed to treat type 2 diabetes does not increase cardiovascular (CV) risk to an unacceptable extent. CV events reported during phase 2 and phase 3 trials should be prospectively and independently adjudicated. Before submission of a new drug application or biologics license application, sponsors should compare the incidence of major CV events occurring with the investigational agent versus the control group to show that the upper bound of the 2-sided 95% confidence interval (CI) for the estimated risk ratio is less than 1.8. If the CI includes 1.3, a postmarketing trial will be necessary to definitively show that the upper bound of the 95% CI for the estimated risk ratio is then less than 1.3. In 2012, the European Medicines Agency (EMA) issued an updated guideline on the clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus that detailed its CV safety assessment requirements. Although similar to the FDA guidance, the EMA guideline does not prospectively define any pre- or postapproval risk margins. This expert perspective, prepared by members of the Cardiac Safety Research Consortium, discusses clinical development strategies, operational issues, and statistical methodological issues to satisfy the FDA's CV safety requirements, and, where appropriate, the EMA guideline. Actual case examples, where applicable, are presented.

Background: Classical patient and tumour characteristics are the benchmark of personalised breast cancer (BC) management. Recent evidence has demonstrated that immune and molecular profiling of BC may also play an important role. Despite evidence of differences between invasive ductal (IDC) and lobular (ILC) BC, they are infrequently accounted for when making treatment decisions for individual patients. The purpose of this study was to investigate the relevance of the tumour immune response in the major histological subtypes of BC. We also assessed the relationship between immune responses and molecular subtypes and their prognostic potential., Methods: Immunostains were done for HLA-I, HLA-E, HLA-G, Tregs, NK cells and CTLs for the composition of the immune profiles and Ki67, EGFR, CK5/6, ER, PR and HER2 for molecular profiles in 714 breast cancer patients who underwent primary surgery., Results: No significant association was found between IDC (90.6%) and ILC (9.4%) and tumour immune subtypes (P=0.4) and molecular subtypes (P=0.4). However, for the relapse-free period (RFP) tumour immune subtyping was prognostic (P=0.002) in IDC, but not ILC. Contrary to ILC, IDC patients frequently expressed higher cleaved caspase-3 and Ki67, which was prognostic. Intermediate immune-susceptible IDC expressing high cleaved caspase-3 or Ki67 showed worse RFP than those with low expression (caspase-3: P=0.004; Ki67: P=0.002); this was not seen for ILC or in high or low immune-susceptible tumour types for either IDC or ILC., Conclusions: Tumour immune characteristics and host immune responses are prognostic in IDC, but not ILC. In addition, tumour immune profiles are only prognostic in Luminal A tumours.

Plant diversity drives changes in the soil microbial community which may result in alterations in ecosystem functions. However, the governing factors between the composition of soil microbial communities and plant diversity are not well understood. We investigated the impact of plant diversity (plant species richness and functional group richness) and plant functional group identity on soil microbial biomass and soil microbial community structure in experimental grassland ecosystems. Total microbial biomass and community structure were determined by phospholipid fatty acid (PLFA) analysis. The diversity gradient covered 1, 2, 4, 8, 16 and 60 plant species and 1, 2, 3 and 4 plant functional groups (grasses, legumes, small herbs and tall herbs). In May 2007, soil samples were taken from experimental plots and from nearby fields and meadows. Beside soil texture, plant species richness was the main driver of soil microbial biomass. Structural equation modeling revealed that the positive plant diversity effect was mainly mediated by higher leaf area index resulting in higher soil moisture in the top soil layer. The fungal-to-bacterial biomass ratio was positively affected by plant functional group richness and negatively by the presence of legumes. Bacteria were more closely related to abiotic differences caused by plant diversity, while fungi were more affected by plant-derived organic matter inputs. We found diverse plant communities promoted faster transition of soil microbial communities typical for arable land towards grassland communities. Although some mechanisms underlying the plant diversity effect on soil microorganisms could be identified, future studies have to determine plant traits shaping soil microbial community structure. We suspect differences in root traits among different plant communities, such as root turnover rates and chemical composition of root exudates, to structure soil microbial communities.

The development of drought tolerant plants is a high priority because the area suffering from drought is expected to increase in the future due to global warming. One strategy for the development of drought tolerance is to genetically engineer plants with transcription factors (TFs) that regulate the expression of several genes related to abiotic stress defense responses. This work assessed the performance of soybean plants overexpressing the TF DREB1A under drought conditions in the field and in the greenhouse. Drought was simulated in the greenhouse by progressively drying the soil of pot cultures of the P58 and P1142 lines. In the field, the performance of the P58 line and of 09D-0077, a cross between the cultivars BR16 and P58, was evaluated under four different water regimes: irrigation, natural drought (no irrigation) and water stress created using rain-out shelters in the vegetative or reproductive stages. Although the dehydration-responsive element-binding protein (DREB) plants did not outperform the cultivar BR16 in terms of yield, some yield components were increased when drought was introduced during the vegetative stage, such as the number of seeds, the number of pods with seeds and the total number of pods. The greenhouse data suggest that the higher survival rates of DREB plants are because of lower water use due to lower transpiration rates under well watered conditions. Further studies are needed to better characterize the soil and atmospheric conditions under which these plants may outperform the non-transformed parental plants.

The loss of soybean yield to Brazilian producers because of a water deficit in the 2011-2012 season was 12.9%. To reduce such losses, molecular biology techniques, including plant transformation, can be used to insert genes of interest into conventional soybean cultivars to produce lines that are more tolerant to drought. The abscisic acid (ABA)-independent Dehydration Responsive Element Binding (DREB) gene family has been used to obtain plants with increased tolerance to abiotic stresses. In the present study, the rd29A:AtDREB2A CA gene from Arabidopsis thaliana was inserted into soybean using biolistics. Seventy-eight genetically modified (GM) soybean lines containing 2-17 copies of the AtDREB2A CA gene were produced. Two GM soybean lines (P1397 and P2193) were analyzed to assess the differential expression of the AtDREB2A CA transgene in leaves and roots submitted to various dehydration treatments. Both GM lines exhibited high expression of the transgene, with the roots of P2193 showing the highest expression levels during water deficit. Physiological parameters examined during water deficit confirmed the induction of stress. This analysis of AtDREB2A CA expression in GM soybean indicated that line P2193 had the greatest stability and highest expression in roots during water deficit-induced stress.

Background: In developed countries, 40% of breast cancer patients are >65 years of age at diagnosis, of whom 16% additionally suffer from diabetes. The aim of this study was to assess the impact of diabetes on relapse-free period (RFP) and overall mortality in elderly breast cancer patients., Patients and Methods: Patients were selected from the retrospective FOCUS cohort, which contains detailed information of elderly breast cancer patients. RFP was calculated using Fine and Gray competing risk regression models for patients with diabetes versus patients without diabetes. Overall survival was calculated by Cox regression models, in which patients were divided into four groups: no comorbidity, diabetes only, diabetes and other comorbidity or other comorbidity without diabetes., Results: Overall, 3124 patients with non-metastasized breast cancer were included. RFP was better for patients with diabetes compared with patients without diabetes (multivariable HR 0.77, 95% CI 0.59-1.01), irrespective of other comorbidity and most evident in patients aged ≥75 years (HR 0.67, 95% CI 0.45-0.98). The overall survival was similar for patients with diabetes only compared with patients without comorbidity (HR 0.86, 95% CI 0.45-0.98), while patients with diabetes and additional comorbidity had the worst overall survival (HR 1.70, 95% CI 1.44-2.01)., Conclusion: When taking competing mortality into account, RFP was better in elderly breast cancer patients with diabetes compared with patients without diabetes. Moreover, patients with diabetes without other comorbidity had a similar overall survival as patients without any comorbidity. Possibly, unfavourable effects of (complications of) diabetes on overall survival are counterbalanced by beneficial effects of metformin on the occurrence of breast cancer recurrences.

In order to predict which ecosystem functions are most at risk from biodiversity loss, meta-analyses have generalised results from biodiversity experiments over different sites and ecosystem types. In contrast, comparing the strength of biodiversity effects across a large number of ecosystem processes measured in a single experiment permits more direct comparisons. Here, we present an analysis of 418 separate measures of 38 ecosystem processes. Overall, 45 % of processes were significantly affected by plant species richness, suggesting that, while diversity affects a large number of processes not all respond to biodiversity. We therefore compared the strength of plant diversity effects between different categories of ecosystem processes, grouping processes according to the year of measurement, their biogeochemical cycle, trophic level and compartment (above- or belowground) and according to whether they were measures of biodiversity or other ecosystem processes, biotic or abiotic and static or dynamic. Overall, and for several individual processes, we found that biodiversity effects became stronger over time. Measures of the carbon cycle were also affected more strongly by plant species richness than were the measures associated with the nitrogen cycle. Further, we found greater plant species richness effects on measures of biodiversity than on other processes. The differential effects of plant diversity on the various types of ecosystem processes indicate that future research and political effort should shift from a general debate about whether biodiversity loss impairs ecosystem functions to focussing on the specific functions of interest and ways to preserve them individually or in combination.

Recent studies assessing the role of biological diversity for ecosystem functioning indicate that the diversity of functional traits and the evolutionary history of species in a community, not the number of taxonomic units, ultimately drives the biodiversity--ecosystem-function relationship. Here, we simultaneously assessed the importance of plant functional trait and phylogenetic diversity as predictors of major trophic groups of soil biota (abundance and diversity), six years from the onset of a grassland biodiversity experiment. Plant functional and phylogenetic diversity were generally better predictors of soil biota than the traditionally used species or functional group richness. Functional diversity was a reliable predictor for most biota, with the exception of soil microorganisms, which were better predicted by phylogenetic diversity. These results provide empirical support for the idea that the diversity of plant functional traits and the diversity of evolutionary lineages in a community are important for maintaining higher abundances and diversity of soil communities.

Intracarotid transplantation has shown potential for efficient stem cell delivery to the brain. However, reported complications, such as compromised cerebral blood flow (CBF), prompted us to perform further safety studies. Glial-restricted precursors (GRPs) and mesenchymal stem cells (MSCs) were transplanted into the internal carotid artery of rats (n=99), using a microcatheter. Magnetic resonance imaging was used to detect post-transplantation complications, including the development of stroke, for the following experimental variables: cell size, cell dose, cell infusion velocity, delay between artery occlusion and cell infusion, discordant versus concordant xenografting, and intracarotid transplantation with preserved versus compromised blood flow. Immunocompatibility and delayed infusion did not affect the number of complications. An infusion velocity over 1 mL/minute often resulted in stroke (27 out of 44 animals), even with an infusion of vehicle, whereas a lower velocity (0.2 mL/minute) was safe for the infusion of both vehicle and smaller cells (GRPs, diameter=15 μm). Infusion of larger cells (MSCs, diameter=25 μm) resulted in a profound decrease (75±17%) in CBF. Stroke lesions occurred frequently (12 out of 15 animals) when injecting 2 × 10(6) MSCs, but not after lowering the dose to 1 × 10(6) cells. The present results show that cell size and infusion velocity are critical factors in developing safe protocols for intracarotid stem cell transplantation.

Background: The TGF-β superfamily members transforming growth factor-β (TGF-β/Activin) and bone morphogenetic proteins (BMP) have been implicated in the pathogenesis of atherosclerosis. However, their role in human disease remains controversial. In this study we used Smad phosphorylation as a read out for TGF-β and BMP signaling during the initiation, progression and (de)stabilization of human atherosclerotic disease., Material and Methods: A systematic analysis was performed in 114 peri-renal aortic patches (stained with Movat Pentachrome, H&E, pSmad2, pSmad1,5,8 and PAI-1) covering the entire atherosclerotic spectrum (van Dijk, 2010). Immunostaining against T-cells (CD3) and monocytes and macrophages (CD68) was used to explore a putative association between TGF-β and BMP signaling and vascular inflammation., Results: Smad phosphorylation was present within the normal arterial wall in approximately 10% of the endothelial cells and intimal smooth muscle cells. A significant increase in pSmad2 and pSmad1,5,8 positivity was found in non-progressive lesions (>50% positivity). No further increase or decrease was found in the progressive atherosclerotic lesions, vulnerable and stabilized lesions. No association was found between TGF-β and BMP signaling and CD3 and CD68 expression, nor cap thickness., Conclusion: Activation of the TGF-β and BMP pathways is an early event in atherosclerotic lesion formation. No significant relationships were found between Smad phosphorylation and vessel wall inflammation or plaque vulnerability.

This study investigated the antimicrobial activities and modes of action of penta-, hexa-, hepta-, octa-, nona-, and deca-O-galloylglucose (gallotannins) isolated from mango kernels. The MICs and minimum bactericidal concentrations (MBCs) against food-borne bacteria and fungi were determined using a critical dilution assay. Gram-positive bacteria were generally more susceptible to gallotannins than were Gram-negative bacteria. The MICs of gallotannins against Bacillus subtilis, Bacillus cereus, Clostridium botulinum, Campylobacter jejuni, Listeria monocytogenes, and Staphylococcus aureus were 0.2 g liter(-1) or less; enterotoxigenic Escherichia coli and Salmonella enterica were inhibited by 0.5 to 1 g liter(-1), and lactic acid bacteria were resistant. The use of lipopolysaccharide mutants of S. enterica indicated that the outer membrane confers resistance toward gallotannins. Supplementation of LB medium with iron eliminated the inhibitory activity of gallotannins against Staphylococcus aureus, and siderophore-deficient mutants of S. enterica were less resistant toward gallotannins than was the wild-type strain. Hepta-O-galloylglucose sensitized Lactobacillus plantarum TMW1.460 to hop extract, indicating inactivation of hop resistance mechanisms, e.g., the multidrug resistance (MDR) transporter HorA. Carbohydrate metabolism of Lactococcus lactis MG1363, a conditionally respiring organism, was influenced by hepta-O-galloylglucose when grown under aerobic conditions and in the presence of heme but not under anaerobic conditions, indicating that gallotannins influence the respiratory chain. In conclusion, the inhibitory activities of gallotannins are attributable to their strong affinity for iron and likely additionally relate to the inactivation of membrane-bound proteins.

Background: One of the most significant consequences of contemporary global change is the rapid decline of biodiversity in many ecosystems. Knowledge of the consequences of biodiversity loss in terrestrial ecosystems is largely restricted to single ecosystem functions. Impacts of key plant functional groups on soil biota are considered to be more important than those of plant diversity; however, current knowledge mainly relies on short-term experiments., Methodology/principal Findings: We studied changes in the impacts of plant diversity and presence of key functional groups on soil biota by investigating the performance of soil microorganisms and soil fauna two, four and six years after the establishment of model grasslands. The results indicate that temporal changes of plant community effects depend on the trophic affiliation of soil animals: plant diversity effects on decomposers only occurred after six years, changed little in herbivores, but occurred in predators after two years. The results suggest that plant diversity, in terms of species and functional group richness, is the most important plant community property affecting soil biota, exceeding the relevance of plant above- and belowground productivity and the presence of key plant functional groups, i.e. grasses and legumes, with the relevance of the latter decreasing in time., Conclusions/significance: Plant diversity effects on biota are not only due to the presence of key plant functional groups or plant productivity highlighting the importance of diverse and high-quality plant derived resources, and supporting the validity of the singular hypothesis for soil biota. Our results demonstrate that in the long term plant diversity essentially drives the performance of soil biota questioning the paradigm that belowground communities are not affected by plant diversity and reinforcing the importance of biodiversity for ecosystem functioning.

Biodiversity is rapidly declining, and this may negatively affect ecosystem processes, including economically important ecosystem services. Previous studies have shown that biodiversity has positive effects on organisms and processes across trophic levels. However, only a few studies have so far incorporated an explicit food-web perspective. In an eight-year biodiversity experiment, we studied an unprecedented range of above- and below-ground organisms and multitrophic interactions. A multitrophic data set originating from a single long-term experiment allows mechanistic insights that would not be gained from meta-analysis of different experiments. Here we show that plant diversity effects dampen with increasing trophic level and degree of omnivory. This was true both for abundance and species richness of organisms. Furthermore, we present comprehensive above-ground/below-ground biodiversity food webs. Both above ground and below ground, herbivores responded more strongly to changes in plant diversity than did carnivores or omnivores. Density and richness of carnivorous taxa was independent of vegetation structure. Below-ground responses to plant diversity were consistently weaker than above-ground responses. Responses to increasing plant diversity were generally positive, but were negative for biological invasion, pathogen infestation and hyperparasitism. Our results suggest that plant diversity has strong bottom-up effects on multitrophic interaction networks, with particularly strong effects on lower trophic levels. Effects on higher trophic levels are indirectly mediated through bottom-up trophic cascades.