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Denitrification, a key process in soil nitrogen cycling, occurs predominantly within microbial hotspots, such as those around particulate organic matter (POM), where denitrifiers use nitrate as an alternative electron acceptor. For accurate prediction of dinitrogen (N 2 ) and nitrous oxide (N 2 O) emissions from denitrification, a precise quantification of these microscale hotspots is required. The distribution of POM is of crucial importance in this context, as the local oxygen (O 2 ) balance is governed not only by its high O 2 demand but also by the local O 2 availability. Employing a unique combination of X-ray CT imaging, microscale O 2 measurements, and 15 N labeling, we were able to quantify hotspots of aerobic respiration and denitrification. We analyzed greenhouse gas (GHG) fluxes, soil oxygen supply, and the distribution of POM in intact soil samples from grassland and cropland under different moisture conditions. Our findings reveal that both proximal and distal POM, identified through X-ray CT imaging, contribute to GHG emissions. The distal POM, i.e. POM at distant locations to air-filled pores, emerged as a primary driver of denitrification within structured soils of both land uses. Thus, the higher denitrification rates in the grassland could be attributed to the higher content of distal POM. Conversely, despite possessing compacted areas that could favor denitrification, the cropland had only small amounts of distal POM to stimulate denitrification in it. This underlines the complex interaction between soil structural heterogeneity, organic carbon supply, and microbial hotspot formation and thus contributes to a better understanding of soil-related GHG emissions. In summary, our study provides a holistic understanding of soil-borne greenhouse gas emissions and emphasizes the need to refine predictive models for soil denitrification and N 2 O emissions by incorporating the microscale distribution of POM., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The lipopolyplex, a multicomponent nonviral gene carrier, generally demonstrates superior colloidal stability, reduced cytotoxicity, and high transfection efficiency. In this study, a new concept, photochemical reaction-induced transfection, using photosensitizer (PS)-loaded lipopolyplexes was applied, which led to enhanced transfection and cytotoxic effects by photoexcitation of the photosensitizer. Hypericin, a hydrophobic photosensitizer, was encapsulated in the lipid bilayer of liposomes. The preformed nanosized hypericin liposomes enclosed the linear polyethylenimine (lPEI)/pDNA polyplexes, resulting in the formation of hypericin lipopolyplexes (Hy-LPP). The diameters of Hy-LPP containing 50 nM hypericin and 0.25 μg of pDNA were 185.6 ± 7.74 nm and 230.2 ± 4.60 nm, respectively, measured by dynamic light scattering (DLS) and atomic force microscopy (AFM). Gel electrophoresis confirmed the encapsulation of hypericin and pDNA in lipopolyplexes. Furthermore, in vitro irradiation of intracellular Hy-LPP at radiant exposures of 200, 600, and 1000 mJ/cm 2 was evaluated. It demonstrated 60- to 75-fold higher in vitro luciferase expression than that in nonirradiated cells. The lactate dehydrogenase (LDH) assay supported that reduced transfection was a consequence of photocytotoxicity. The developed photosensitizer-loaded lipopolyplexes improved the transfection efficiency of an exogenous gene or induced photocytotoxicity; however, the frontier lies in the applied photochemical dose. The light-triggered photoexcitation of intracellular hypericin resulted in the generation of reactive oxygen species (ROS), leading to photoselective transfection in HepG2 cells. It was concluded that the two codelivered therapeutics resulted in enhanced transfection and a photodynamic effect by tuning the applied photochemical dose.

Spider silk is a tough and versatile biological material combining high tensile strength and extensibility through nanocomposite structure and its nonlinear elastic behaviour. Notably, spiders rarely use single silk fibres in isolation, but instead process them into more complex composites, such as silk fibre bundles, sheets and anchorages, involving a combination of spinneret, leg and body movements. While the material properties of single silk fibres have been extensively studied, the mechanical properties of silk composites and meta-structures are poorly understood and exhibit a hereto largely untapped potential for the bio-inspired design of novel fabrics with outstanding mechanical properties. In this study, we report on the tensile mechanics of the adhesive capture threads of the Southern house spider ( Kukulcania hibernalis ), which exhibit extreme extensibility, surpassing that of the viscid capture threads of orb weavers by up to tenfold. By combining high-resolution mechanical testing, microscopy and in silico experiments based on a hierarchical modified version of the Fibre Bundle Model, we demonstrate that extreme extensibility is based on a hierarchical loops-on-loops structure combining linear and coiled elements. The stepwise unravelling of the loops leads to the repeated fracture of the connected linear fibres, delaying terminal failure and enhancing energy absorption. This principle could be used to achieve tailored fabrics and materials that are able to sustain high deformation without failure., Competing Interests: We declare we have no competing interests., (© 2024 The Authors.)

Competing Interests: SS is on the advisory boards of the following companies: Abbott, Dexcom, Menarini, Medtronic, Roche, Sanofi, Lilly, Glooko and received speaking fees from Berlin-Chemie, Dexcom, Lilly, Medtronic, Menarini, Novo, Roche.DD received remuneration from Ascensia Diabetes, Insulet, Roche Diagnostics and is a member of the Advisory Boards of Ascensia Diabetes, Glooko, Lilly.BG has received speaking and consulting fees from Ascensia, Dexcom, Diabeloop, Insulet, Lilly, Novartis, NovoNordisk, Medtronic, Roche, Vitalaire. KL states that she has served on Advisory Boards of Abbott, Roche Diabetes Care and Biomarin within the past 3 years, and has also received speaking honoraria from Astra Zeneca, BDI, BioMarin, Chiesi, Fachkommission Bayern, Glooko, Insulet, Lilly Deutschland, Medtronic, Menarini Berlin Chemie, Merck Serono, MSD SHARP & DOHME, NovoNordisk, Roche Diabetes Care, Sanofi-Aventis.SVS has participated in Advisory Boards of: Abbott, Dexcom, Insulet, Lilly, Medtronic and Novo Nordisk. SVS has received speaking fees from Abbott, Berlin-Chemie, Dexcom, Hexal/Sandoz, Infectopharm, Lilly, Medtronic, Merck-Serono, Novo Nordisk and Sanofi-Aventis.AT is an independent consultant, expert in CGM systems and diabetes technology, until April 2020 he was the scientific director of Medtronic Diabetes Germany, since then he has received grants and lecture fees from the companies Evivamed, Dexcom, Abbott, Berlin-Chemie, Novo-Nordisk, Sanofi.RZ is a member of the Advisory Boards of the following companies: Abbott, Dexcom, MySugr, NovoNordisk, Roche Diabetes Care and Vertex, and received speaking fees from Abbott, Dexcom, Glooko, Medtronic, NovoNordisk and Roche Diabetes Care as well as VitalAire.GF is general manager and medical director of the Institute for Diabetes Technology, Research and Development Company at the University of Ulm, Ulm, Germany, which carries out clinical studies e.g. with medical devices for diabetes therapy on its own initiative and on behalf of various companies.GF/IfDT have received research support, speakers’ honoraria or consulting fees in the last 3 years from Abbott, Ascensia, Berlin Chemie, Boydsense, Dexcom, Lilly Deutschland, Novo Nordisk, Perfood, Pharamsens, Roche, Sinocare, Terumo, Ypsomed.

The 2017 EULAR/ACR classification criteria for adult/juvenile idiopathic inflammatory myopathies (IIM) were established using a data-driven approach by an international group of myositis experts to allow classification of IIM and its major subtypes. Since their publication, the performance of the criteria has been tested in multiple cohorts worldwide and significant limitations have been identified. Moreover, the understanding and classification of IIM have evolved since 2017. This scoping review was undertaken as part of a large international project to revise the EULAR/ACR criteria and aims to i) summarise the evidence from the current literature on the performance characteristics of the 2017 EULAR/ACR classification criteria in various cohorts and IIM subtypes, and ii) delineate the factors that need to be considered in the revision of the classification criteria. A systematic search of Medline (via PubMed), Cumulative Index to Nursing and Allied Health Literature, and conference abstract archives was conducted independently by three investigators for studies on the EULAR/ACR criteria published between October 2017 and January 2023. This scoping review of 19 articles and 13 abstracts revealed overall good performance characteristics of the EULAR/ACR criteria for IIM, yet deficiencies in lack of inclusion of certain IIM subtypes, such as immune mediated necrotising myopathy, amyopathic dermatomyositis, antisynthetase syndrome and overlap myositis. Published modifications that may improve the performance characteristics of the criteria for classification of IIM subtypes were also summarised. The results of this review suggest that a revision of the EULAR/ACR criteria is warranted.

Antisynthease syndrome (ASSD) is a rare, complex and understudied autoimmune disease. Internet-based studies can overcome barriers of traditional on-site research and are therefore very appealing for rare diseases. The aim of this study was to investigate patient-reported symptoms, diagnostic delay, symptoms, medical care, health status, working status, disease knowledge and willingness to participate in research of ASSD patients by conducting an international web-based survey. The multilingual questionnaire was created by an international group of rheumatologists and patients and distributed online. 236 participants from 22 countries completed the survey. 184/236 (78.0%) were female, mean age (SD) was 49.6 years (11.3) and most common antisynthetase antibody was Jo-1 (169/236, 71.6%). 79/236 (33.5%) reported to work full-time. Median diagnostic delay was one year. The most common symptom at disease onset was fatigue 159/236 (67.4%), followed by myalgia 130/236 (55.1%). The complete triad of myositis, arthritis and lung involvement verified by a clinician was present in 42/236 (17.8%) at disease onset and in 88/236 (37.3%) during the disease course. 36/236 (15.3%) reported to have been diagnosed with fibromyalgia and 40/236 (16.3%) with depression. The most reported immunosuppressive treatments were oral corticosteroids 179/236 (75.9%), followed by rituximab 85/236 (36.0%). 73/236 (30.9%) had received physiotherapy treatment. 71/236 (30.1%) reported to know useful online information sources related to ASSD. 223/236 (94.5%) were willing to share health data for research purposes once a year. Our results reiterate that internet-based research is invaluable for cooperating with patients to foster knowledge in rare diseases., (© 2023. The Author(s).)

Borderline personality disorder (BPD) is among the most severe mental health problems with long-lasting deterioration of functioning. According to a Cochrane review, evidence for methods focused on treatment for adolescent BPD patients is very limited. Aims of the study were to demonstrate the noninferiority of adolescent identity treatment (AIT) compared with dialectical behavior therapy for adolescents (DBT-A), and that intensive early treatment of BPD leads to significant improvement of psychosocial and personality functioning in adolescent patients. In a nonrandomized controlled trial using a noninferiority approach, we compared 37 patients treated with DBT-A with 23 patients treated with AIT. Both treatments included 25 weekly individual psychotherapy sessions and five to eight family sessions. Patients were assessed at four timepoints: baseline, posttreatment, 1- and 2-year follow-up. Primary outcome was psychosocial functioning at 1-year follow-up. We performed both intention-to-treat analyses and per-protocol analyses (completers). Baseline characteristics of both groups were not significantly different except for age and self-injurious behavior. In all, six AIT patients (26%) and 10 DBT-A patients (27%) dropped out of treatment. Both DBT-A and AIT significantly improved adolescents' psychosocial functioning (AIT: d = 1.82; DBT-A: d = 1.73) and personality functioning. BPD criteria and depression were significantly reduced by both treatments. Overall, AIT was found to be not inferior to DBT-A and even more efficient in reducing BPD criteria. Both treatments are highly effective in improving psychosocial functioning and personality functioning in adolescent BPD patients. AIT is a promising approach and not inferior to DBT-A in respect to treatment efficiency. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Examining in situ processes in the soil rhizosphere requires spatial information on physical and chemical properties under undisturbed conditions. We developed a correlative imaging workflow for targeted sampling of roots in their three-dimensional (3D) context and assessed the imprint of roots on chemical properties of the root-soil contact zone at micrometer to millimeter scale. Maize ( Zea mays ) was grown in 15 N-labeled soil columns and pulse-labeled with 13 CO 2 to visualize the spatial distribution of carbon inputs and nitrogen uptake together with the redistribution of other elements. Soil columns were scanned by X-ray computed tomography (X-ray CT) at low resolution (45 μm) to enable image-guided subsampling of specific root segments. Resin-embedded subsamples were then analyzed by X-ray CT at high resolution (10 μm) for their 3D structure and chemical gradients around roots using micro-X-ray fluorescence spectroscopy (μXRF), nanoscale secondary ion mass spectrometry (NanoSIMS), and laser-ablation isotope ratio mass spectrometry (LA-IRMS). Concentration gradients, particularly of calcium and sulfur, with different spatial extents could be identified by μXRF. NanoSIMS and LA-IRMS detected the release of 13 C into soil up to a distance of 100 μm from the root surface, whereas 15 N accumulated preferentially in the root cells. We conclude that combining targeted sampling of the soil-root system and correlative microscopy opens new avenues for unraveling rhizosphere processes in situ .

Introduction: The aim of the study was to analyze the results of intraocular surgery in treated retinoblastoma eyes and to assess the long-term results with a priority on local recurrences, secondary enucleation, and metastases. Methods: Retrospective noncomparative case series. Results: From March 1964 to January 2020, 42 eyes of 40 retinoblastoma patients underwent intraocular surgery. Time interval between the last therapy and surgery was 9.5 years (mean: 114 months; median: 54.5 months). 31 eyes were treated for radiogenic cataract formation with a gain in visual acuity of 61.3%. One child developed an upper eyelid metastasis, 3 showed second primary malignancies (SPM), one a late recurrence, and 2 eyes were enucleated. Retinal surgery was performed in 17 eyes; 6 eyes were done as a combined procedure. Indications were radiogenic complications in the sense of a vitreous hemorrhage in 11 eyes and a rhegmatogenous retinal detachment in 6 eyes. 41.2% of the treated eyes had a postoperative gain in visual acuity, whereas 9.5% of the eyes could not be preserved in the long term. Regarding systemic involvement 2 patients developed late recurrences and one a SPM. Conclusion: Surgical therapy in treated retinoblastoma is necessary in isolated cases. In our series, cataract surgery was a safe procedure with a good option of a significant increase in visual acuity. As expected, vitreoretinal treated eyes showed a limited gain in visual acuity, a higher risk of late recurrences, and a lower globe retention rate. Therefore, a careful indication and individual risk-benefit analysis are mandatory., (© 2022 S. Karger AG, Basel.)

Objectives: As described recently, intravenously injected gadolinium-based contrast agent (GBCA) penetrates into the anterior eye chamber (AC) and is drained from the retina to the distal optic nerve (ON) along perivascular spaces, which serves retinal homeostasis and was termed the orbital glymphatic system (GS). Independently, AC enhancement predicted ON infiltration, a major risk factor for advanced retinoblastoma (RB), in a small RB patient cohort. We aimed to review the supposed imaging biomarker for ON infiltration in a large RB cohort and with respect to the recently described orbital GS., Methods: This IRB-approved retrospective single-center study encompassed 539 orbital MRIs performed with an orbital coil and with the children under general anesthesia. Differences of signal intensity ratios (∆SIRs) of the AC to the lens were determined between non-contrast and GBCA-enhanced T1-weighted images and were correlated with histopathologic presence of ON infiltration., Results: ∆SIR of the RB eye was an independent, significant predictor for ON invasion in multivariate analysis with adjustment for tumor size (p < 0.05) and increased with infiltration level., Conclusions: GBCA enhancement of the AC predicts ON infiltration. This might be caused by impairment of the orbital glymphatic system, which is supposed to clear toxic metabolites from the retina to the postlaminar ON. In RB with ON infiltration, this efflux path is likely to be inhibited, which is supposed to result in disturbed retinal homeostasis, release of vascular endothelial growth factor, and iris neovascularization, which increases penetration of GBCA into the AC., Key Points: • Infiltration of the optic nerve can be predicted by anterior chamber enhancement after intravenous MRI contrast agent administration. • Increased anterior chamber enhancement in retinoblastoma with optic nerve infiltration might result from dysfunction of the orbital glymphatic system with disturbance of retinal homeostasis and consecutive iris neovascularization., (© 2022. The Author(s).)

Competing Interests: SS received lecturing fees from Abbott, Ascensia, Astra Zeneca, Berlin-Chemie, Dexcom, Lilly, Menarini, Medtronic, MSD, Novo Nordisk, Roche, Sanofi, Ypsomed Advisory Adboards: Abbott, Dexcom, Diabeloop, Lilly, Medtronic, Roche. DD is on advisory boards of the following companies and have received speaking fees from Abbott, Ascensia, Menarini, Roche, Profusa, Senseonics. BG: Lecture Fees and / or advisory boards of Dexcom, Diabeloop, Medtronic, Roche, Vitalaire. KL reports being a consultant for Abbott, Medtronic, Sanofi-Aventis, and having received lecture fees from Astra Zeneca, BDI, BioMarin, Chiesi, Insulet, Lilly Deutschland, Medtronic, Menarini Berlin Chemie, MSD SHARP & DOHME, neubourg skin care, NovoNordisk, Roche Diabetes Care, Sanofi-Aventis, with no potential conflicts of interest relevant to this article. SVS is on advisory boards of the following companies: Abbott, Dexcom, Insulet, Lilly, Medtronic and Novo Nordisk and has received speaking fees from Abbott, Berlin-Chemie, Dexcom, Hexal, Infectopharm, Lilly, Medtronic, Merck, Novo Nordisk and Sanofi. AT was scientific director of Medtronic Germany, manufacturer and distributor of insulin pumps and CGM systems (till april 2020). He is on advisory boards of the following companies: Evivamed, Dexcom. He've got speaking fees from Berlin-Chemie, Dexcom, Novo Nordisk and Sanofi. RZ is on advisory boards of the following companies: Abbott, Lilly, Novo and Roche and has received speaking fees from Abbott, Dexcom, Lilly, Menarini, Novo and Roche. GF is general manager and medical director of the Insitute for Diabetes Technology (Institut für Diabetes-Technologie Forschungs- und Entwicklungsgesellschaft mbH an der Universität Ulm, Ulm, Germany), which carries out clinical studies e.g. with medical devices for diabetes therapy on its own initiative and on behalf of various companies. GF/IDT have received speakers’ honoraria or consulting fees from Abbott, Ascensia, Berlin Chemie, Beurer, BOYDsense, CRF Health, Dexcom, i-SENS, Lilly, Metronom, MySugr, Novo Nordisk, Pharmasens, Roche, Sanofi, Sensile, Terumo, Ypsomed.

Oxygenic photosynthesis evolved in cyanobacteria, primary producers of striking ecological importance. Like plants, cyanobacteria use the Calvin-Benson-Bassham cycle for CO 2 fixation, fuelled by ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO). In a competitive reaction this enzyme also fixes O 2 which makes it rather ineffective. To mitigate this problem, cyanobacteria evolved a CO 2 concentrating mechanism (CCM) to pool CO 2 in the vicinity of RuBisCO. However, the regulation of these carbon (C) assimilatory systems is understood only partially. Using the model Synechocystis sp. PCC 6803 we characterized an essential LysR-type transcriptional regulator encoded by gene sll0998. Transcript profiling of a knockdown mutant revealed diminished expression of several genes involved in C acquisition, including rbcLXS, sbtA and ccmKL encoding RuBisCO and parts of the CCM, respectively. We demonstrate that the Sll0998 protein binds the rbcL promoter and acts as a RuBisCO regulator (RbcR). We propose ATTA(G/A)-N 5 -(C/T)TAAT as the binding motif consensus. Our data validate RbcR as a regulator of inorganic C assimilation and define the regulon controlled by it. Biological CO 2 fixation can sustain efforts to reduce its atmospheric concentrations and is fundamental for the light-driven production of chemicals directly from CO 2 . Information about the involved regulatory and physiological processes is crucial to engineer cyanobacterial cell factories., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

Since the introduction of fast-track surgery in the field of arthroplasty, all disciplines involved have been challenged with the task of close and continuous joint communication in the context of daily routine care. Processes that have been agreed upon interdisciplinarily must be reviewed at regular intervals, and, if necessary, adapted and newly agreed upon with the aim of optimizing the perioperative risks both medically and along the therapeutic pathway. The responsibility of the anaesthesiologist is not only limited to the performance of anaesthesia, but also includes the care of patients with a view to optimal pain therapy, maintenance of homeostasis and ensuring a rapid return of the patient's self-determination., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Soil carbon sequestration arises from the interplay of carbon input and stabilization, which vary in space and time. Assessing the resulting microscale carbon distribution in an intact pore space, however, has so far eluded methodological accessibility. Here, we explore the role of soil moisture regimes in shaping microscale carbon gradients by a novel mapping protocol for particulate organic matter and carbon in the soil matrix based on a combination of Osmium staining, X-ray computed tomography, and machine learning. With three different soil types we show that the moisture regime governs C losses from particulate organic matter and the microscale carbon redistribution and stabilization patterns in the soil matrix. Carbon depletion around pores (aperture > 10 µm) occurs in a much larger soil volume (19-74%) than carbon enrichment around particulate organic matter (1%). Thus, interacting microscale processes shaped by the moisture regime are a decisive factor for overall soil carbon persistence., (© 2022. The Author(s).)

Purpose: The aim of this study was to report the efficacy of combined intravitreal chemotherapy (IVC) and ruthenium-106 brachytherapy in retinoblastoma, either as first-line or second-line treatment, following systemic chemoreduction or intra-arterial chemotherapy., Methods: Retrospective data of 18 eyes from 18 patients treated with IVC and brachytherapy from August 2014 to December 2019 were collected., Results: The method described was our first-line therapy in 6 patients, whereas it was used as second-line treatment after chemoreduction in the remaining 12 patients. The eyes showed the following classification at initial presentation: 2 group B eyes, 3 group C eyes, and 13 group D eyes. The mean follow-up was 19.5 months (range 2-53 months). The mean patient age at brachytherapy was 34.0 months (range 15-83 months). The median prescribed dose at the tumour base and apex was 574.5 ± 306.7 Gy and 88.5 ± 12.2 Gy, respectively. The ocular retention rate was 66.7%. Six eyes had to be enucleated due to uncontrollable subretinal and recurrent vitreous seeding, tumour relapse, recurrence of a solid tumour elsewhere in the eye, and persistent vitreous bleeding with loss of tumour control. The mean number of intravitreal injections of melphalan was 5.0. Two patients received a simultaneous injection of topotecan for insufficient therapeutic response. With regard to radiogenic complications, we could observe temporary retinal and vitreous bleeding (27.8%), serous retinal detachment (44.4%), and radiogenic maculopathy and retinopathy (11.1%). None of the children showed metastatic disease during follow-up., Conclusion: Ruthenium-106 plaque therapy in combination with IVC is an effective local therapy with good tumour control rates even in advanced eyes. Overall, the analysed therapeutic approach shows an acceptable side-effect profile, especially when considering that external-beam radiation therapy and systemic polychemotherapy or at least the number of cycles needed, with their increased incidence of adverse events, can thus be avoided., Competing Interests: M.S. obtained research funding to the institution from AstraZeneca and honoraria (advisory board function) from AstraZeneca, Bristol-Myers Squibb, Sanofi-Aventis, and Janssen-Cilag. The other authors have no conflict of interest to disclose., (Copyright © 2021 by S. Karger AG, Basel.)

Background: Eye-preserving therapy in retinoblastoma comprises systemic chemotherapy, but studies analyzing the efficacy of different chemotherapy regimens are scarce., Methods: The efficacy and side effects of two different eye-preserving chemotherapy regimens containing either vincristine, etoposide, and carboplatin (VEC) or cyclophosphamide, vincristine, etoposide, and carboplatin (CyVEC) were compared in a prospective non-interventional observational study including children diagnosed with retinoblastoma between 2013 and 2019 in Germany and Austria. Event-free eye survival (EFES) and overall eye survival (OES) of all 164 eyes treated with both regimens and risk factors were investigated., Results: The EFES after VEC (2-year EFES 72.3%) was higher than after CyVEC (2-year EFES 50.4%) (p logrank  < .001). The OES did not differ significantly between the two treatment groups (p logrank  = .77; 2-year OES VEC: 82.1% vs. CyVEC: 84.8%). Advanced International Classification of Retinoblastoma (ICRB) group was prognostic for a lower EFES (p logrank  < .0001; 2-year EFES ICRB A/B/C 71.3% vs. ICRB D/E 43.0%) and OES (p logrank  < .0001; 2-year OES ICRB A/B/C 93.1% vs. ICRB D/E 61.5%). The multivariate analysis showed that age at diagnosis older than 12 months and ICRB A/B/C were associated with better EFES. No second malignancies or ototoxicities were reported after a follow-up of median 3.1 years after diagnosis of retinoblastoma (range 0.1-6.9 years)., Conclusions: Despite omitting cyclophosphamide, the EFES was higher after VEC chemotherapy that contains higher doses of carboplatin compared to CyVEC. The major risk factor for enucleation was advanced ICRB tumor grouping. Randomized clinical trials on efficacy and side effects of eye-preserving chemotherapy are required to tailor treatment protocols for retinoblastoma patients., (© 2021 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

In stressful situations such as the COVID-19-pandemic, unpleasant emotions are expected to increase while pleasant emotions will likely decrease. Little is known about the role cognitive appraisals, information management, and upregulating pleasant emotions can play to support emotion regulation in a pandemic. In an online survey (N = 1682), we investigated predictors of changes in pleasant and unpleasant emotions in a German sample (aged 18-88 years) shortly after the first restrictions were imposed. Crisis self-efficacy and felt restriction were predictors of changes in unpleasant emotions and joy alike. The application of emotion up-regulation strategies was weakly associated with changes in joy. Among the different upregulation strategies, only "savouring the moment" predicted changes in joy. Our study informs future research perspectives assessing the role of upregulating pleasant emotions under challenging circumstances., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Patient suicidality is a frequently experienced topic for psychotherapists. Especially adolescents with borderline personality pathology (BPP) often exhibit suicidal tendencies. Previous research which examined therapists' countertransference towards suicidal patients suggested that therapists are negatively affected and distressed by them. We hypothesize that this emotional response of the therapists is related to specific sessions in which suicidality came up as a topic. Accordingly, the objective of this study consists in examining therapists' emotional state on a session level of analysis., Methods: The sample consisted of N = 21 adolescents (age 13-19 years) with BPD or subthreshold BPD. Therapists' emotional states were measured in n = 418 sessions using the Session Evaluation Questionnaire. Principal component analysis was used to reduce dimensionality of the therapist response. The emotional states were compared depending on whether suicidality has been addressed in the session (SS) or not (NSS)., Results: Two components could be identified. Firstly, therapists were more aroused, excited, afraid, angry and uncertain after SS than after NSS. Secondly, therapists were more aroused, excited, definite and pleased after SS than after NSS., Discussion: Suicidality does not always have to be a burden for therapists: Both a "distress" and an "eustress" component occur in this context from which the latter is supposed to help clinicians master a difficult situation. Since countertransference feelings are often not fully conscious, it is necessary to do research on therapists' emotional states after sessions in which suicidality is addressed. This is crucial to both prevent the therapeutic process from being endangered and preserve clinicians' mental health. Clinical implications and limitations are discussed., (© 2021. The Author(s).)

Background: Adequate management of retinoblastoma requires a multidisciplinary and individual approach to treatment. Intraarterial chemotherapy (IAC) is one of the most commonly used treatment modalities, and enables supraselective application of chemotherapy via the ophthalmic artery and is now established in almost all treatment centres. However, published treatment success rates are heterogeneous. There are some unanswered issues regarding sight-threatening ocular complications and the long-term occurrence of secondary malignancies and metastatic disease. The objective of the present study is to analyse the results of a German national reference centre., Methods: Retrospective analysis of all children with an indication for at least one IAC from April 2010 to April 2020. IAC was used either as primary or recurrence therapy. Obligatory follow-up was at least 6 months., Results: 137 eyes of 127 children with an indication for IAC could be included. 12 eyes with a follow-up of less than 6 months and 37 eyes in which IAC was technically not feasible were excluded. In summary, 88 eyes of 79 children were finally analysed. Mean follow-up was 38 months, ranging from 7 to 117 months. In total, 195 procedures were completed. In 30 eyes (34.1%) IAC was conducted as primary and in 58 (65.9%) as secondary therapy. There was an initial IAC treatment response in 75 eyes (85.2%) with a recurrence-free rate of 61.3%. Eye salvage rate was 68.1% with 28 enucleated eyes in total. Ocular complications were observed in 36 eyes (40.9%), with 19 eyes (21.6%) showing severe sight-threatening and 11 eyes (12.5%) presenting minor non-sight-threatening toxic reactions. During follow-up, 1 child developed a secondary malignancy, 1 child developed metastasis and 1 child died as a consequence of trilateral retinoblastoma., Conclusion: In summary, IAC is a potent modality for retinoblastoma treatment and has been very successful, even in advanced disease and heavily pretreated eyes. However, ocular complications should be taken in consideration, especially when the only seeing eye is treated. Long term incidences of secondary malignancies and metastatic diseases should be further investigated in prospective studies., Competing Interests: The authors declare that they have no conflict of interest./Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Retinoblastoma and other eye tumors in childhood are rare diseases. Many eye tumors are the first signs of a genetic tumor predisposition syndrome and the affected children carry a higher risk of developing other cancers later in life. Clinical and genetic data of all children with eye tumors diagnosed between 2013-2018 in Germany and Austria were collected in a multicenter prospective observational study. In five years, 300 children were recruited into the study: 287 with retinoblastoma, 7 uveal melanoma, 3 ciliary body medulloepithelioma, 2 retinal astrocytoma, 1 meningioma of the optic nerve extending into the eye. Heritable retinoblastoma was diagnosed in 44% of children with retinoblastoma. One child with meningioma of the optic nerve extending into the eye was diagnosed with neurofibromatosis 2. No pathogenic constitutional variant in DICER1 was detected in a child with medulloepithelioma while two children did not receive genetic analysis. Because of the known association with tumor predisposition syndromes, genetic counseling should be offered to all children with eye tumors. Children with a genetic predisposition to cancer should receive a tailored surveillance including detailed history, physical examinations and, if indicated, imaging to screen for other cancer. Early detection of cancers may reduce mortality.

Despite the increased risk of subsequent primary tumors (SPTs) external beam radiation (EBRT) may be the only therapeutic option to preserve a retinoblastoma eye. Due to their physical properties, proton beam therapy (PBT) offers the possibility to use the effectiveness of EBRT in tumor treatment and to decisively reduce the treatment-related morbidity. We report our experiences of PBT as rescue therapy in a retrospectively studied cohort of 15 advanced retinoblastoma eyes as final option for eye-preserving therapy. The average age at the initiation of PBT was 35 (14-97) months, mean follow-up was 22 (2-46) months. Prior to PBT, all eyes were treated with systemic chemotherapy and a mean number of 7.1 additional treatments. Indication for PBT was non-feasibility of intra-arterial chemotherapy (IAC) in 10 eyes, tumor recurrence after IAC in another 3 eyes and diffuse infiltrating retinoblastoma in 2 eyes. Six eyes (40%) were enucleated after a mean time interval of 4.8 (1-8) months. Cataract formation was the most common complication affecting 44.4% of the preserved eyes, yet 77.8% achieved a visual acuity of >20/200. Two of the 15 children treated developed metastatic disease during follow-up, resulting in a 13.3% metastasis rate. PBT is a useful treatment modality as a rescue therapy in retinoblastoma eyes with an eye-preserving rate of 60%. As patients are at lifetime risk of SPTs consistent monitoring is mandatory.

Background: X-ray computed tomography is acknowledged as a powerful tool for the study of root system architecture of plants growing in soil. In this paper, we improved the original root segmentation algorithm "Rootine" and present its succeeding version "Rootine v.2". In addition to gray value information, Rootine algorithms are based on shape detection of cylindrical roots. Both algorithms are macros for the ImageJ software and are made freely available to the public. New features in Rootine v.2 are (i) a pot wall detection and removal step to avoid segmentation artefacts for roots growing along the pot wall, (ii) a calculation of the root average gray value based on a histogram analysis, (iii) an automatic calculation of thresholds for hysteresis thresholding of the tubeness image to reduce the number of parameters and (iv) a false negatives recovery based on shape criteria to increase root recovery. We compare the segmentation results of Rootine v.1 and Rootine v.2 with the results of root washing and subsequent analysis with WinRhizo. We use a benchmark dataset of maize roots (Zea mays L. cv. B73) grown in repacked soil for two scenarios with differing soil heterogeneity and image quality., Results: We demonstrate that Rootine v.2 outperforms its preceding version in terms of root recovery and enables to match better the root diameter distribution data obtained with root washing. Despite a longer processing time, Rootine v.2 comprises less user-defined parameters and shows an overall greater usability., Conclusion: The proposed method facilitates higher root detection accuracy than its predecessor and has the potential for improving high-throughput root phenotyping procedures based on X-ray computed tomography data analysis.

One of the questions yet to be fully understood is to what extent the properties of the sensory and the movement information interact to facilitate sensorimotor integration. In this study, we examined the relative contribution of the continuity compatibility between motor goals and their sensory outcomes in timing variability. The variability of inter-response intervals was measured in a synchronization-continuation paradigm. Participants performed two repetitive movement tasks whereby they drew circles either using continuous or discontinuous self-paced movements while receiving discrete or continuous auditory feedback. The results demonstrated that the effect of perceptual-motor continuity compatibility may be limited in self-paced auditory-motor synchronization as timing variability was not significantly influenced by the continuity of the feedback or the continuity compatibility between feedback and the movement produced. In addition, results suggested that the presence of salient perceptual events marking the completion of the time intervals elicited a common timing process in both continuous and discontinuous circle drawing, regardless of the continuity of the auditory feedback. These findings open a new line of investigation into the role of the discriminability and reliability of the event-based information in determining the nature of the timing mechanisms engaged in continuous and discontinuous self-paced rhythmic movements., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Silence in psychotherapy has been associated with different, sometimes opposing meanings. This study investigated silence during adolescent identity treatment in adolescent patients with borderline personality pathology. A more active therapeutic approach with less silence is advised in adolescent identity treatment. It was hypothesized that a session with more silence might be negatively perceived by adolescent patients. A total of 382 sessions that involved 21 female patients were analyzed. Silence was automatically detected from audio recordings. Diarization (segmenting an audio according to speaker identity) was performed. The patient's perception of the sessions was measured with the Session Evaluation Questionnaire. The amount of silence in the different speaker-switching patterns was not independent of one other. This finding supports the hypothesis of mutual attunement of patient and therapist concerning the amount of silence in a given session. Sessions with less silence were rated as being both smoother and better. The potential implications for clinical practice are discussed. The investigation of turn-taking and interpersonal temporal dynamics is relevant for psychotherapy research. The topic can be addressed efficiently using automated procedures. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Aims: Comprehensive knowledge, specific skills and data-analysis competences are prerequisites for the successful use of continuous glucose monitoring (CGM) systems. SPECTRUM is a structured training programme for real-time CGM (rtCGM) consisting of a web-based introduction and six group sessions of 90 min each. The 'CGM-TRAIN study' evaluated the efficacy and acceptance of SPECTRUM and rtCGM systems among adults with insulin therapy., Methods: Participants (n = 120) were recruited from 10 German diabetes centres in which they were treated under usual care conditions. Outcome measures were rtCGM knowledge, practical skills, satisfaction with the training programme, satisfaction and acceptance of rtCGM system and glycaemic control. Data were collected at study entry, after training completion and at 6-month follow-up., Results: All participants were diagnosed with type 1 diabetes (56% women, mean age 42.4 ± 13.4 years, diabetes duration 21.6 ± 11.6 years), 110 participants completed the course. After training completion, rtCGM-specific knowledge had improved by 43% (scale: 0-40 points) from 21.2 ± 7.6 to 30.4 ± 4.5 points; p < 0.001. The knowledge-level persisted until follow-up (29.4 ± 4.5). Participants were able to master nearly all the practical requirements of the technology. In addition, rtCGM was highly accepted, and participants were motivated to use their systems continuously. HbA 1c improved slightly from 61 ± 14 mmol/mol (7.7 ± 1.3%) before training to 60 ± 14 mmol/mol (7.6 ± 1.3%) at follow-up (p = 0.04). The training programme itself was favourably rated by participants., Conclusions: Under usual out-patient daily care conditions, the training programme SPECTRUM improved knowledge and skills about rtCGM in adults with type 1 diabetes. This was associated with a reduced HbA 1c , high satisfaction and acceptance of rtCGM (Clinical Trials Registry no.: DRKS00014380)., (© 2020 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Restoration of upper limb motor function and patient functional independence are crucial treatment targets in neurological rehabilitation. Growing evidence indicates that music-based intervention is a promising therapeutic approach for the restoration of upper extremity functional abilities in neurologic conditions such as cerebral palsy, stroke, and Parkinson's Disease. In this context, music technology may be particularly useful to increase the availability and accessibility of music-based therapy and assist therapists in the implementation and assessment of targeted therapeutic goals. In the present study, we conducted a pre-clinical, single-arm trial to evaluate a novel music-based therapeutic device (SONATA) for upper limb extremity movement training. The device consists of a graphical user interface generated by a single-board computer displayed on a 32" touchscreen with built-in speakers controlled wirelessly by a computer tablet. The system includes two operational modes that allow users to play musical melodies on a virtual keyboard or draw figures/shapes whereby every action input results in controllable sensory feedback. Four motor tasks involving hand/finger movement were performed with 21 healthy individuals (13 males, aged 26.4 ± 3.5 years) to evaluate the device's operational modes and main features. The results of the functional tests suggest that the device is a reliable system to present pre-defined sequences of audiovisual stimuli and shapes and to record response and movement data. This preliminary study also suggests that the device is feasible and adequate for use with healthy individuals. These findings open new avenues for future clinical research to further investigate the feasibility and usability of the SONATA as a tool for upper extremity motor function training in neurological rehabilitation. Directions for future clinical research are discussed., Competing Interests: TBJ and VV declare no competing interests. RP and SS are employed engineers at BeSB GmbH Berlin, and NS currently serves as unpaid consultant and informal scientific advisor for BeSB GmbH Berlin. The device presented and tested in this study is a product developed in collaboration between BeSB and MT with potential for commercialization. This commercial affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials.

The variety of retinal tumors ranges from harmless lesions to benign, locally destructive tumors and life-threatening diseases, and they are not always easy to distinguish from each other. The differential diagnosis includes real neoplasia, reactive inflammatory pathologies and vascular anomalies of the fundus as well. If possible, the diagnosis should be made clinically in order to avoid the danger of tumor cell spread via invasive diagnostic tools. Nevertheless, genetic analysis of the pathology is gaining more importance and adds to the precise characterization of the diagnosis. Depending on the tumor entity, therapy in a specialized center is necessary., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein. Erklärung zu nichtfinanziellen Interessen Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The scientific and clinical interest in children with mentally ill parents increased in the last years. Those children belong to a high risk population so that prevention is urgently indicated. Due to genetic influences and partly to an impairment of the parent-child interaction because of the parent's illness there exists a higher risk for child abuse. They show a three to five time increased risk to develop mental problems which require treatment over the course of their lives. They show abnormalities in social, cognitive and emotional areas. Untreated mental disorders and associated behavioral problems in children often chronify and lead to permanent impairment of the emotional, social and also intellectual development. Early detection and treatment are indicated and of high relevance.

The IPAT/Kaya identity is the most popular index used to analyze the driving forces of individual factors on CO 2 emissions. It represents the CO 2 emissions as a product of factors, such as the population, gross domestic product (GDP) per capita, energy intensity of the GDP, and carbon footprint of energy. In this study, we evaluated the mutual relationship of the factors of the IPAT/Kaya identity and their decomposed variables with the fossil-fuel CO 2 flux, as measured by the Greenhouse Gases Observing Satellite (GOSAT). We built two regression models to explain this flux; one using the IPAT/Kaya identity factors as the explanatory variables and the other one using their decomposed factors. The factors of the IPAT/Kaya identity have less explanatory power than their decomposed variables and comparably low correlation with the fossil-fuel CO 2 flux. However, the model using the decomposed variables shows significant multicollinearity. We performed a multivariate cluster analysis for further investigating the benefits of using the decomposed variables instead of the original factors. The results of the cluster analysis showed that except for the M factor, the IPAT/Kaya identity factors are inadequate for explaining the variations in the fossil-fuel CO 2 flux, whereas the decomposed variables produce reasonable clusters that can help identify the relevant drivers of this flux., Competing Interests: The authors declare no conflict of interest.

A new method combining online nano solid phase extraction coupled with Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was developed to extract and analyze organic matter (OM) from microliter volumes of salt containing soil solution samples. This approach allows the reproducible analysis of only minute amounts of organic carbon (down to 10 ng C) without the need of further sample preparation. The new method was applied to unravel developing small-scale patterns of dissolved organic matter (DOM) in soil solutions of a soil column experiment in which Zea mays plants were grown for 3 weeks. Soil solution was sampled by micro suction cups from the undisturbed soil-root system once a week. Growth of the root system and, hence, position of individual roots relative to the suction cups was followed by X-ray computed tomography (X-ray CT). Our method makes it possible to resolve the chemical complexity of soil solution OM (up to 4300 molecular formulas from 2.5 μL sample). This allows to observe chemical gradients in the rhizosphere on a molecular level over time. The increasing influence of roots on soil solution OM is visible from higher molecular masses, an increasing degree of oxygenation and a higher fraction of formulas containing heteroatoms. The online nano solid phase extraction-FT-ICR-MS method provides novel insight into the processes affecting DOM in the rhizosphere, such as root exudation, microbial processes, and soil organic matter stabilization.

Background: To demonstrate histopathological findings in retinoblastoma eyes enucleated after intra-arterial chemotherapy (IAC) with special emphasis on vascular toxicity and local tumour control., Methods: Retrospective study with a consecutive series of 23 retinoblastoma eyes enucleated after IAC where histopathological work-up was available., Results: From November 2010 to June 2019 23 eyes were enucleated after the attempt of eye salvaging therapy with IAC using melphalan. IAC was the first line treatment in nine and salvage treatment in 14 eyes. Doses of melphalan ranged from 3 to 7.5 mg, whereby a strict protocol with age-appropriate dosage was not used until 2015. The mean number of treatment cycles was 1.8. The main indications for enucleation were poor treatment response or tumour progression in 14 eyes, severe vascular complications in five eyes and a total exudative retinal detachment with amaurosis in the remaining four eyes. We found active disease in 15 eyes with an indication for adjuvant chemotherapy due to high risk factors for metastases in four eyes. To date none of these patients developed metastatic disease. Concerning vascular toxicity, we detected a central retinal artery occlusion in three eyes, severe vasculitis in another three, ischaemic outer retina atrophy and choroidal ischaemia in seven eyes with one eye developing a severe proliferative retinopathy., Conclusion: IAC is a highly effective treatment option for advanced retinoblastoma, but the described potential risks should be kept in mind. These include severe vascular complications, as well as the possibility of persisting vital tumour cells fulfilling high-risk criteria for adjuvant chemotherapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Given the rarity of retinoblastoma and the consequences of accidental vitrectomy in the event of misdiagnosis, reporting on clinical experience in this area is important., Objective: The aim of this study was to analyse the management and complications with a focus on local orbital recurrence and metastatic disease in 10 children vitrectomized in an undetected retinoblastoma eye., Methods: This is a retrospective descriptive case series conducted in a single-centre referral university hospital., Results: From October 1991 to June 2019, 10 patients with a vitrectomy in an unsuspected retinoblastoma eye were included in this study. The main preoperative diagnoses were unilateral inflammation with a suspected lymphoma, uveitis or toxocariasis in 5 cases, vitreous haemorrhage after trauma in 2 cases, and the last 3 were misdiagnosed with Coats disease, rhegmatogenous retinal detachment and congenital cataract. Mean age at surgery was 3 years, ranging from 14 months to 6 and a half years. Nine patients were suffering from unilateral retinoblastoma; these were enucleated and treated with 4-6 cycles of chemotherapy and/or radiation therapy. The sclerotomy sites were infiltrated with tumour cells in 3 cases. In 1 patient, the differential diagnosis of a malignant medulloepithelioma could not be excluded. One patient had bone marrow infiltration on initial presentation; all other patients are healthy without any signs of orbital recurrence or metastatic disease with a mean follow-up of 5.4 years., Conclusion: In children, intraocular tumours, including retinoblastoma and medulloepithelioma, should be ruled out before pars plana vitrectomy is performed. If no doubtless preoperative diagnosis can be established, preoperative magnetic resonance imaging is mandatory. If a vitrectomy in a retinoblastoma eye has been performed, immediate enucleation of the eye with subsequent chemotherapy and orbital radiation is effective to avoid local recurrence and systemic metastases., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 by S. Karger AG, Basel.)

Alliance Ruptures in the Psychotherapy of Adolescents with Borderline Personality Pathology: Risk or Benefit? Adolescents with subthreshold or full-blown borderline personality disorders (borderline personality pathology (BPP)) are characterized by a pronounced instability in their self-image and their interpersonal relationships. The building of a stable therapeutic relationship is considerably challenged in patients with BPP. The concept of alliance ruptures and resolutions assumes that the resolution of ongoing relationship difficulties contributes to therapeutic change. Resolutions are strategies of the therapist to address ruptures, to explore their meaning with the patient and to enhance the therapeutic collaboration between the patient and the therapist. This article illustrates the use and benefits of alliance ruptures and resolutions among adolescents with BPP treated with the manualized treatment concept Adolescent Identity Treatment (AIT). Ten patients were treated with AIT. Three out of ten patients dropped out of treatment prematurely. A total of 187 therapy sessions were analyzed using the Rupture and Resolution Rating System (3RS; Eubanks, Lubitz, Muran, Safran, 2018). Alliance ruptures and resolutions are illustrated in session transcripts of a qualitative case vignette. Quantitative analyses show that alliance ruptures occur frequently over the complete treatment course in good outcome patients. However, frequent alliance ruptures at the beginning of treatment represent a risk for premature treatment termination. The concept of alliance ruptures and resolutions may help to improve the ongoing therapeutic alliance in the treatment of adolescents with BPP.

We propose two preprocessing algorithms suitable for climate time series. The first algorithm detects outliers based on an autoregressive cost update mechanism. The second one is based on the wavelet transform, a method from pattern recognition. In order to benchmark the algorithms' performance we compare them to existing methods based on a synthetic data set. Eventually, for exemplary purposes, the proposed methods are applied to a data set of high-frequent temperature measurements from Novi Sad, Serbia. The results show that both methods together form a powerful tool for signal preprocessing: In case of solitary outliers the autoregressive cost update mechanism prevails, whereas the wavelet-based mechanism is the method of choice in the presence of multiple consecutive outliers., Competing Interests: No potential conflict of interest was reported by the authors., (© 2019 Informa UK Limited, trading as Taylor & Francis Group.)

Competing Interests: LH is active as a consultant in the development of new diagnostic options for various companies (e.g. Roche Diagnostics, Sanofi, Abbott). He is a shareholder and consultant in Profil – Institut für Stoffwech- selforschung, Neuss, and ProSciento, San Diego, USA.DD received lecture fees from Abbott, Dexcom, Lilly, Menarini, Novo Nordisk, Roche Diagnostics, Senseonics and is a member of advisory boards of BD, Profusa, Roche and Senseonics.TS received lecture fees from Abbott, Ascensia, Astra Zeneca/Bristol- Myers Squibb, Bayer, Berlin-Chemie, Boehringer Ingelheim, Eli Lilly, Medtronic, MSD, Novartis, Novo Nordisk, Sanofi. He is a member of advisory boards of Abbott, Ascensia, Bayer Vital, Boehringer Ingelheim, Eli Lilly, Janssen, Medtronic, MSD, Novo Nordisk, Sanofi and has received support for scientific projects from: Astra Zeneca/Bristol-Myers Squibb, Becton Dickinson, Eli Lilly, MSD, Novo Nordisk, Sanofi.SVS has worked as a consultant for Abbott, Dexcom, Lilly, Medtronic, NovoNordisk and Roche for the past 3 years. SVS has received lecture fees and travel expenses from the following companies in the last 3 years: Abbott, Berlin-Chemie, BPI, Lilly, Merck-Serono, Medtronic, NovoNordisk and Pfizer. MN was a consultant and speaker for the following companies: Abbott, Berlin- Chemie, MSD, Sanofi, Medtronic, Bayer Diagnostics, Astra Zeneca. SvS is in an advisory function on the Advisory Board for the optimisation of aids, medicines and information materials for children with diabetes for several companies (Abbott, Eli Lilly, Medtronic, Novo Nordisk, Dexcom). In the last 2 years she has received lecture fees from Abbott, Berlin Chemie, Eli Lilly, Medtronic, Merck, Novo Nordisk, Roche and Sanofi. KL received lecture fees from Astra Zeneca, BDI, Lilly Deutschland, Medtronic, Menarini/Berlin-Chemie, Merck Serono, MSD SHARP & DOHME, Novo Nordisk, Roche Diabetes Care, Sanofi-Aventis. She is a member of the Advisory Boards of Roche Diabetes Care, Medtronic, Dexcom and Sanofi-Aventis. GF is the medical director of IDT (Institut für Diabe tes-Technologie Forschungs- und Entwicklungsgesellschaft mbH at the University of Ulm, Ulm), which carries out clinical studies on medical products for diabetes therapy on its own initiative or on behalf of various companies. GF/IDT has received lecture/consultation fees from Abbott, Ascensia, Dexcom, LifeScan, Menarini Diagnostics, Metronom Health, Novo Nordisk, Roche, Sanofi, Sensile and Ypsomed.

Contradictory evidence exists regarding whether and to which extend roots change soil structure in their vicinity. Here we attempt to reconcile disparate views allowing for the two-way interaction between soil structure and root traits, i.e. changes in soil structure due to plants and changes in root growth due to soil structure. Porosity gradients extending from the root/biopore surface into the bulk soil were investigated with X-ray µCT for undisturbed soil samples from a field chronosequence as well as for a laboratory experiment with Zea mays growing into three different bulk densities. An image analysis protocol was developed, which enabled a fast analysis of the large sample pool (n > 300) at a resolution of 19 µm. Lab experiment showed that growing roots only compact the surrounding soil if macroporosity is low and dominated by isolated pores. When roots can grow into a highly connected macropore system showing high connectivity the rhizosphere is more porous compared to the bulk soil. A compaction around roots/biopores in the field chronosequence was only observed in combination with high root/biopore length densities. We conclude that roots compact the rhizosphere only if the initial soil structure does not offer a sufficient volume of well-connected macropores.

Jeremy Safran and his research group suggest that rupture-repair processes are important for the therapeutic change in patients with personality disorders. In this exploratory study, we describe alliance ruptures and resolutions on a session-by-session basis in a clinical sample of adolescents with Borderline Personality Pathology (BPP). Three research questions are addressed: i) Is there a typical trajectory of alliance ruptures over treatment time? ii) Which rupture and resolution markers occur frequently? iii) Which rupture markers are most significant for the therapeutic alliance? Ten patients who presented with identity diffusion and at least three Borderline Personality Disorder criteria were studied and treated with Adolescent Identity Treatment. Alliance ruptures and resolutions were coded in 187 therapy sessions according to the Rupture Resolution Rating System. Mixed-effect models were used for statistical analyses. Findings supported an inverted U-shaped trajectory of alliance ruptures across treatment time. The inspection of individual trajectories displayed that alliance ruptures emerge non-linearly with particular significant alliance ruptures appearing in phases or single peak sessions. Withdrawal rupture markers emerged more often compared to confrontation markers. However, confrontation markers inflicted a higher impact or strain on the immediate collaboration between patient and therapist compared to withdrawal markers. Clinicians should expect alliance ruptures to occur frequently in the treatment of adolescents with BPP. The findings support the theory of a dynamic therapeutic alliance characterised by a continuous negotiation between patients and therapists., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest., (©Copyright: the Author(s), 2019.)

The microenvironmental conditions in soil exert a major control on many ecosystem functions of soil. Their investigation in intact soil samples is impaired by methodological challenges in the joint investigation of structural heterogeneity that defines pathways for matter fluxes and biogeochemical heterogeneity that governs reaction patterns and microhabitats. Here we demonstrate how these challenges can be overcome with a novel protocol for correlative imaging based on image registration to combine three-dimensional microstructure analysis of X-ray tomography data with biogeochemical microscopic data of various modalities and scales (light microscopy, fluorescence microscopy, electron microscopy, secondary ion mass spectrometry). Correlative imaging of a microcosm study shows that the majority (75%) of bacteria are located in mesopores (<10 μm). Furthermore, they have a preference to forage near macropore surfaces and near fresh particulate organic matter. Ignoring the structural complexity coming from the third dimension is justified for metrics based on size and distances but leads to a substantial bias for metrics based on continuity. This versatile combination of imaging modalities with freely available software and protocols may open up completely new avenues for the investigation of many important biogeochemical and physical processes in structured soils.

Underage patients with Borderline Personality Pathology (BPP) are in need of specialised psychotherapeutic treatment. A handful of these treatments, including Adolescent Identity Treatment (AIT) and Dialectical Behavior Therapy for Adolescents (DBT-A), have been adapted for adolescent patients. Psychotherapy research has shown that the outcome of different psychotherapeutic approaches can be very similar despite conceptual and practical differences between the theoretical models. Therefore, to understand what really works in psychotherapy, it is necessary to investigate the psychotherapeutic process and its effects on the patient. This paper presents a study design for process-outcome research, integrating (1) a classical outcome design, comparing AIT and DBT-A in a non-inferiority trial assessing changes in psychosocial functioning at 12 months after baseline as primary outcome; and (2) a process research design, addressing multiple BPP and psychotherapy relevant factors. These factors include well-studied generic variables such as the psychotherapeutic alliance, more recent approaches such as video-based identification of significant therapeutic events, as well as more experimental approaches such as psychophysiological markers measured during the therapeutic sessions. The use of repeated measures and the methodological pluralism which includes event and micro-process analyses has been recommended for psychotherapy research aiming at a better understanding of the interplay of factors at work to narrow the gap between research and practice in this field.

Over the last 60 years, soil microbiologists have accumulated a wealth of experimental data showing that the bulk, macroscopic parameters (e.g., granulometry, pH, soil organic matter, and biomass contents) commonly used to characterize soils provide insufficient information to describe quantitatively the activity of soil microorganisms and some of its outcomes, like the emission of greenhouse gasses. Clearly, new, more appropriate macroscopic parameters are needed, which reflect better the spatial heterogeneity of soils at the microscale (i.e., the pore scale) that is commensurate with the habitat of many microorganisms. For a long time, spectroscopic and microscopic tools were lacking to quantify processes at that scale, but major technological advances over the last 15 years have made suitable equipment available to researchers. In this context, the objective of the present article is to review progress achieved to date in the significant research program that has ensued. This program can be rationalized as a sequence of steps, namely the quantification and modeling of the physical-, (bio)chemical-, and microbiological properties of soils, the integration of these different perspectives into a unified theory, its upscaling to the macroscopic scale, and, eventually, the development of new approaches to measure macroscopic soil characteristics. At this stage, significant progress has been achieved on the physical front, and to a lesser extent on the (bio)chemical one as well, both in terms of experiments and modeling. With regard to the microbial aspects, although a lot of work has been devoted to the modeling of bacterial and fungal activity in soils at the pore scale, the appropriateness of model assumptions cannot be readily assessed because of the scarcity of relevant experimental data. For significant progress to be made, it is crucial to make sure that research on the microbial components of soil systems does not keep lagging behind the work on the physical and (bio)chemical characteristics. Concerning the subsequent steps in the program, very little integration of the various disciplinary perspectives has occurred so far, and, as a result, researchers have not yet been able to tackle the scaling up to the macroscopic level. Many challenges, some of them daunting, remain on the path ahead. Fortunately, a number of these challenges may be resolved by brand new measuring equipment that will become commercially available in the very near future.

The rhizosphere, the fraction of soil altered by plant roots, is a dynamic domain that rapidly changes during plant growth. Traditional approaches to quantify root growth patterns are very limited in estimating this transient extent of the rhizosphere. In this paper we advocate the analysis of root growth patterns from the soil perspective. This change of perspective addresses more directly how certain root system architectures facilitate the exploration of soil. For the first time, we propose a parsimonious root distance model with only four parameters which is able to describe root growth patterns throughout all stages in the first 3 weeks of growth of Vicia faba measured with X-ray computed tomography. From these models, which are fitted to the frequency distribution of root distances in soil, it is possible to estimate the rhizosphere volume, i.e., the volume fraction of soil explored by roots, and adapt it to specific interaction distances for water uptake, rhizodeposition, etc. Through 3D time-lapse imaging and image registration it is possible to estimate root age dependent rhizosphere volumes, i.e., volumes specific for certain root age classes. These root distance models are a useful abstraction of complex root growth patterns that provide complementary information on root system architecture unaddressed by traditional root system analysis, which is helpful to constrain dynamic root growth models to achieve more realistic results.

Competing Interests: LH is active as a consultant for various companies (e.g. Roche Diagnostics, Sanofi, Abbott) in the development of new diagnostic options. He is a shareholder and advisor at Profil – Institut für Stoffwechselforschung, Neuss, as well as ProSciento, San Diego, USA. DD received remuneration from Abbott, Dexcom, Medtronic, Novo, Roche, Senseonics and is a member of the Advisory Boards of Becton Dickinson, Roche and Senseonics. TS received remuneration from Abbott, Ascensia, Astra Zeneca/Bristol- Myers Squibb, Bayer, Berlin Chemie, Boehringer Ingelheim, Eli Lilly, Medtronic, MSD, Novartis, Novo Nordisk, and Sanofi. He is a member of the Advisory Boards of Abbott, Ascensia, Bayer Vital, Boehringer Ingelheim, Eli Lilly, Janssen, Medtronic, MSD, Novo Nordisk, and Sanofi and has received support for scientific projects from: Astra Zeneca/Bristol- Myers Squibb, Becton Dickinson, Eli Lilly, MSD, Novo Nordisk, and Sanofi. SS received remuneration from Abbott, Dexcom, Roche Diagnostics, Astra Zeneca, Novo Nordisk, MSD, and Berlin Chemie. She is a member of the Advisory Boards of Abbott, Roche Diagnostics. MN was an advisor and speaker for the following companies: Abbott, Berlin Chemie, MSD, Sanofi, Medtronic, Bayer Diagnostics, and Astra Zeneca. SvS has taken on an advisory/Advisory Board position for many companies (Abbott, Eli Lilly, Medtronic, Novo Nordisk, Roche) is active in optimizing medical aid, medicine and informative literature for children with diabetes. In the past 2 years she has received remuneration from Eli Lilly, Medtronic, Merck, Novo Nordisk, Roche and Sanofi. KL received remuneration from Bayer, BDI, Lilly Deutschland, Medtronic, Menarini/Berlin Chemie, Merck Serono, MSD SHARP & DOHME, Novo Nordisk, Roche Diabetes Care, and Sanofi. She is a member of the Advisory Boards of Roche Diabetes Care, Novo Nordisk, and Sanofi-Aventis. GF is the medical head and director of the IDT (Institut für Diabetes- Technologie Forschungs- und Entwicklungsgesellschaft mbH an der Universität Ulm, Ulm (Institute for Diabetes Technology, Research and Development, Ulm University)), which performs clinical studies on medical products for diabetes therapy either of its own initiative or on behalf of various companies. GF/IDT received/receives remuneration/consultancy fees from Abbott, Ascensia, Bayer, Berlin-Chemie, Becton-Dickinson, Dexcom, LifeScan, Menarini Diagnostics, Novo Nordisk, Roche, Sanofi, Sensile and Ypsomed.

Global change contributes to the retreat of glaciers at unprecedented rates. The deglaciation facilitates biogeochemical processes on glacial deposits with initiating soil formation as an important driver of evolving ecosystems. The underlying mechanisms of soil formation and the association of soil organic matter (SOM) with mineral particles remain unclear, although further insights are critical to understand carbon sequestration in soils. We investigated the microspatial arrangement of SOM coatings at intact soil microaggregate structures during various stages of ecosystem development from 15 to >700 years after deglaciation in the proglacial environment of the Damma glacier (Switzerland). The functionally important clay-sized fraction (<2 μm) was separated into two density fractions with different amounts of organo-mineral associations: light (1.6-2.2 g/cm 3 ) and heavy (>2.2 g/cm 3 ). To quantify how SOM extends across the surface of mineral particles (coverage) and whether SOM coatings are distributed in fragmented or connected patterns (connectivity), we developed an image analysis protocol based on nanoscale secondary ion mass spectrometry (NanoSIMS). We classified SOM and mineral areas depending on the 16 O - , 12 C - , and 12 C 14 N - distributions. With increasing time after glacial retreat, the microspatial coverage and connectivity of SOM increased rapidly. The rapid soil formation led to a succession of patchy distributed to more connected SOM coatings on soil microaggregates. The maximum coverage of 55% at >700 years suggests direct evidence for SOM sequestration being decoupled from the mineral surface, as it was not completely masked by SOM and retained its functionality as an ion exchange site. The chemical composition of SOM coatings showed a rapid change toward a higher CN:C ratio already at 75 years after glacial retreat, which was associated with microbial succession patterns reflecting high N assimilation. Our results demonstrate that rapid SOM sequestration drives the microspatial succession of SOM coatings in soils, a process that can stabilize SOM for the long term., (© 2017 John Wiley & Sons Ltd.)

X-ray CT is a powerful technology to study root growth in soil in-situ. Root systems can be studied in its true 3D geometry over time. Hence, the same plant can be scanned multiple times during development. A downside is the potential of X-rays to interfere with biological processes and therefore plant growth. The aim of this study is to evaluate the influence of cumulative X-ray dose on Vicia faba and Hordeum vulgare during a growth period of 17 days. One control treatment without X-ray scanning was compared to two treatments being scanned every two and four days, respectively. Scanned treatments received a maximum cumulative dose of less than 8 Gy. Plant species differed in their susceptibility to X-ray dose. For Vicia faba, mean total root length was reduced significantly. Leave growth was reduced as well. Number and length of second order laterals was reduced significantly, as well as length of first order laterals. Hordeum vulgare showed no negative impact of X-ray dose on any of the root parameters. Large differences between the two species investigated were detected in respect to susceptibility to X-ray dose. Results indicate that for X-ray CT studies involving temporal resolution a control treatment without scanning is required.

AIT (Adolescent Identity Treatment) - an Integrative Treatment Model for the Treatment of Personality Disorders Personality disorders are patterns of maladaptive personality traits that have an impact on the individual throughout the life span. Borderline Personality Disorder (BPD) is a very severe, but treatable mental disorder. Identity disturbance is seen as the central construct for detecting severe personality pathology - and, most notably, borderline personality disorder - in adults and adolescents. Crises in the development of identity usually resolve into a normal and consolidated identity with flexible and adaptive functioning whereas identity diffusion is viewed as a lack of integration of the concept of the self and significant others. It is seen as the basis for subsequent personality pathology, including that of borderline personality disorder. Although BPD has its onset in adolescence and emerging adulthood the diagnosis is often delayed. In most cases, specific treatment is only offered late in the course of the disorder and to relatively few individuals. Adolescent Identity Treatment (AIT) is a treatment model that focuses on identity pathology as the core characteristic of personality disorders. This model integrates specific techniques for the treatment of adolescent personality pathology on the background of object-relation theories and modified elements of Transference-Focused Psychotherapy. Moreover, psychoeducation, a behavior-oriented homeplan and intensive family work is part of AIT.