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A novel method for close-proximity formation flying under differential atmospheric drag using Coulomb forces is investigated for applications in Earth sensing, space-situational awareness (SSA), and aeronomy. Objects in LEO are supersonic with respect to the ambient environment, creating a thinned out wake region behind the craft as it travels through the ionosphere. Objects within this wake experience little drag acceleration and are able to attain voltages much greater than in the ambient ionospheric plasma, creating implications for the design and control of close-proximity leader–follower spacecraft pairs. The proposed system consists of a leader craft with a set of affixed, conducting spheres and a charged follower craft located in the wake of the leader. The differential drag acceleration between the leader and follower craft is countered by a controlled Coulomb repulsion to maintain precise separation. The charged structure on the rear of the leader craft is designed such that the charged follower craft sits in an electrostatic potential well which opposes off-axis perturbations. A conceptual method for controlling such a pair without the use of propellant using a set of charged spheres is investigated, with nonlinear models of the system’s relative motion derived and discussed. Linearized models are used to demonstrate the local controllability of the system to demonstrate the proposed system’s merit. This linear analysis is used to derive conditions on controllability and control performance under different charge geometries and environmental assumptions.

In recent years there has been a great deal of research and development pertaining to the landing of spacecraft on small bodies, such as asteroids. The capabilities to identify and avoid large rock...

Self-actuated deployable space structures present a novel challenge for deployment dynamics modeling efforts, where the system-level influence of strain energy components must be captured. Here, th...

The electrostatic tractor has been proposed to touchlessly remove space debris from geosynchronous orbit by taking advantage of intercraft Coulomb forces. A controlled spacecraft (tug) emits an ele...

This work explores on-board planning for the single spacecraft, multiple ground station Earth-observing satellite scheduling problem through artificial neural network function approximation of stat...

Purpose This guideline provides evidence-based recommendations for the indications and technique-dose of external beam radiation therapy (EBRT) in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC). Methods The American Society for Radiation Oncology convened a task force to address 5 key questions focused on the indications, techniques, and outcomes of EBRT in HCC and IHC. It is intended to cover the definitive, consolidative, salvage, preoperative (including bridge to transplant), and adjuvant settings as well as palliative EBRT for symptomatic primary lesions. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. Results Strong recommendations are made for using EBRT as a potential first-line treatment in patients with liver-confined HCC who are not candidates for curative therapy, consolidative therapy after incomplete response to liver-directed therapies, and as a salvage option for local recurrences. The guideline conditionally recommends EBRT for patients with liver-confined multifocal or unresectable HCC, or those with macrovascular invasion, sequenced with systemic or catheter-based therapies. Palliative EBRT is conditionally recommended for symptomatic primary HCC and/or macrovascular tumor thrombi. EBRT is conditionally recommended as a bridge to transplant or prior to surgery in carefully selected patients. For patients with unresectable IHC, consolidative EBRT with or without chemotherapy should be considered, typically after systemic therapy. Adjuvant EBRT is conditionally recommended for resected IHC with high-risk features. Selection of dose-fractionation regimen and technique should be based on disease extent, disease location, underlying liver function, and available technologies. Conclusions The task force has proposed recommendations to inform best clinical practices on the use of EBRT for HCC and IHC with strong emphasis on multidisciplinary care. Future studies should focus on further defining the role of EBRT in the context of liver-directed and systemic therapies and refining optimal regimens and techniques.

Numerous missions are being proposed which involve multiple spacecraft operating in close proximity in harsh charging environments. In such missions, the ability to sense the electrostatic potentia...

The overuse of fertilizers in agriculture and their entry into freshwater has many negative impacts on biodiversity and poses problems for drinking water resources in Germany. In response to exceeding levels of nitrate concentrations in groundwater in parts of the country, an intense public dispute evolved and a significant policy change in fertilizer regulation occurred in 2020. Based on the German case of agricultural water pollution, this study demonstrates in an innovative way how discourse network analysis is a fruitful method for the integrated study of actor coalitions and their use of narrative strategies in public debate. Theoretically, the study draws on the narrative policy framework (NPF) to explain how actor coalitions use narrative strategies to attempt to influence policymaking on water pollution by agricultural activities. The empirical analysis builds on newspaper articles and press releases disseminated between 2010 and 2020. The results demonstrate how two opposing actor coalitions with congruent policy beliefs formed in the struggle over fertilizer regulation. These not only diverged in their policy beliefs but also differed in their use of narrative strategies to try to expand or contain the policy issue. More precisely, the coalitions adapted their narratives over time in response to changes in the likelihood to win or lose. Furthermore, the results suggest the coalition in favor of stricter fertilizer regulation was more sophisticated in its effort to mobilize specific target groups. Overall, the article provides a valuable contribution to the literature on the NPF by combining research on coalition formation and policy narratives. Supplementary Information The online version contains supplementary material available at 10.1007/s11077-021-09439-x.

Leadership is a frequently used term, but these uses include various definitions and applications; these uses are sometimes contradictory. This definitional vagueness can be a particular challenge for professions, including social work. In comparison to other similar professions, there is a lack of leadership knowledge generation in social work. In addition, the organisational context in England has been challenging in recent decades, likely hindering development and application of leadership models. Health care has a broader empirical and conceptual development of leadership as a topic of examination. In health care literature, compassionate leadership is gaining momentum as a useful way of developing good clinical leadership. There is a strong tradition in social work of engaging with compassion as an element of social work values. We present models of compassionate leadership and consider their usefulness for the current social work knowledge base. We suggest that compassionate leadership may prove useful for social work practice and academia.

Concerns about child physical and digital safety are emerging with families' adoption of smart home technologies such as robot vacuums and smart speakers. To better understand parents' definitions and perceptions of child safety regarding smart home technologies, we interviewed 23 parents who are smart home adopters. We contribute insights into parents' perceptions of the physical and digital safety risks smart home technologies pose to children, and how such perceptions formed and changed across three phases. In acquiring smart home devices, parents already considered whether the device could cause physical harm to their children or pose privacy and security risks. Once children become active users of smart home technologies, parents however reported encountering unanticipated physical safety risks and digital safety issues (e.g., exposure to unsuitable content) that required their mitigation strategies. As their children grow up, parents further expressed the need to shift attention from physical safety to digital safety. Parents' safety perceptions influence how they involve children in smart home interactions and implement mitigation strategies, such as restricting access to certain devices and using parental controls. We identify six factors that shape parents' perception and evaluation of smart home safety risks to children, including parenting style, parents' tech-savviness, parents' trust in tech companies, children's age and developmental differences, news media, and device characteristics. We provide design and policy recommendations to better protect children's safety in the smart home environment.

Zusammenfassung Ziel der Studie Zahlreiche Studien weisen auf ein breites Spektrum häufig gleichzeitig auftretender psychischer Störungen wie jene der Generalisierten Angststörung bei der Behandlung von Personen mit Cannabiskonsumstörungen hin (GAD). Bisherige Internet-basierte Studien konnten zwar vereinzelt die Reduktion von Cannabiskonsum zeigen, berücksichtigten aber keine komorbide Störungen. Ziel des E-Coach gestützten Online-Selbsthilfeprogramm CANreduce 2.0 ist die Reduzierung des Cannabiskonsums und der gegebenenfalls vorhandenen GAD. Methodik Sekundäranalyse der in der Allgemeinbevölkerung rekrutierten Cannabiskonsumierenden der CANreduce 2.0 Studie der beiden aktiven Interventionsgruppen (N=367). Für die Analysen wurden diese Teilnehmende aufgrund ihres erreichten Symptomatik-Wertes der General Anxiety Disorder Scale (GAD-7) in 4 Gruppen eingeteilt: Minimale (GAD-7 Werte: 0–4; N=102), Milde (5–9; N=151), Moderate (10–14; N=78) und Schwere (15–21; N=36) Angststörung und anschliessend ihre Behandlungsverläufe mittels Intention-to-Treat Analysen bezüglich ihrer Cannabiskonsumtage und ihrer Werte auf dem Cannabis Use Disorder Identification Test (CUDIT), der Severity of Dependence Scale (SDS), der GAD-7, der Center of Epidemiologic Studies of Depression Scale (CES-D) sowie bezüglich ihrer Adhärenz verglichen. Ergebnisse Alle 4 Gruppen reduzierten unabhängig von ihrer GAD-Symptomatik die Anzahl ihrer Cannabiskonsumtage, ihren CUDIT und SDS Score sowohl 6 Wochen als auch 3 Monate nach der Baselineerhebung. Weiter haben mit Ausnahme von der minimalen GAD-7-Gruppe alle Gruppen eine Reduktion der Angstsymptomatik nach 3 Monaten aufgewiesen. Analog zeigten mit Ausnahme der minimalen GAD-7-Gruppe alle GAD-7-Gruppen eine deutliche Reduktion in der depressiven Symptomatik. Bezüglich der gemessenen Adhärenz zeigten sich keine Unterschiede zwischen den GAD-7-Gruppen. Schlussfolgerungen CANreduce 2.0 scheint sowohl den Cannabiskonsum, die Ausprägung der Cannabiskonsumstörung bzw. die Cannabisabhängigkeit wie auch eine gegebenenfalls vorhandene GAD-Symptomatik zu reduzieren.

CXCL10 is a promising early noninvasive diagnostic marker for allograft rejection and predictive for long-term outcomes. However, its value when measured later in the posttransplant course has not yet been accurately analyzed.We investigated urinary CXCL10 in 141 patients from a prospective, observational renal transplant cohort with 182 clinically indicated allograft biopsies performed12 months posttransplant and corresponding urines. Urinary CXCL10 was retrospectively quantified on stored urines using the MSD V-Plex Chemokine Panel 1 sandwich immunoassay (Meso Scale Discovery). The primary outcome was a composite of allograft loss/renal function decline (30% estimated glomerular filtration rate [eGFR]-decrease between index biopsy and last follow-up).Seventy-two patients (51%) reached the primary outcome, and their urinary CXCL10 levels were significantly higher at the time of their biopsy compared with patients with stable allograft function (median 9.3 ng/mmol vs 3.3 ng/mmol, P.0001). Time-to-endpoint analyses according to high/low urinary CXCL10 demonstrated that low urinary CXCL10 (≤7.0 ng/mmol) was associated with 73% 5-year event-free graft survival compared with 48% with high urinary CXCL10 (7.0 ng/mmol; P = .0001). Even in histologically quiescent patients, high urinary CXCL10 was associated with inferior endpoint-free graft survival (P = .003), and it was an independent predictor of the primary outcome (P = .03).This study demonstrates that urinary CXCL10 has a promising diagnostic performance for detection of late allograft rejection and is an independent predictor of long-term renal allograft outcomes, even in histologically quiescent patients.

Kidney fibrosis constitutes the shared final pathway of nearly all chronic nephropathies, but biomarkers for the non-invasive assessment of kidney fibrosis are currently not available. To address this, we characterize five candidate biomarkers of kidney fibrosis: Cadherin-11 (CDH11), Sparc-related modular calcium binding protein-2 (SMOC2), Pigment epithelium-derived factor (PEDF), Matrix-Gla protein, and Thrombospondin-2. Gene expression profiles in single-cell and single-nucleus RNA-sequencing (sc/snRNA-seq) datasets from rodent models of fibrosis and human chronic kidney disease (CKD) were explored, and Luminex-based assays for each biomarker were developed. Plasma and urine biomarker levels were measured using independent prospective cohorts of CKD: the Boston Kidney Biopsy Cohort, a cohort of individuals with biopsy-confirmed semiquantitative assessment of kidney fibrosis, and the Seattle Kidney Study, a cohort of patients with common forms of CKD. Ordinal logistic regression and Cox proportional hazards regression models were used to test associations of biomarkers with interstitial fibrosis and tubular atrophy and progression to end-stage kidney disease and death, respectively. Sc/snRNA-seq data confirmed cell-specific expression of biomarker genes in fibroblasts. After multivariable adjustment, higher levels of plasma CDH11, SMOC2, and PEDF and urinary CDH11 and PEDF were significantly associated with increasing severity of interstitial fibrosis and tubular atrophy in the Boston Kidney Biopsy Cohort. In both cohorts, higher levels of plasma and urinary SMOC2 and urinary CDH11 were independently associated with progression to end-stage kidney disease. Higher levels of urinary PEDF associated with end-stage kidney disease in the Seattle Kidney Study, with a similar signal in the Boston Kidney Biopsy Cohort, although the latter narrowly missed statistical significance. Thus, we identified CDH11, SMOC2, and PEDF as promising non-invasive biomarkers of kidney fibrosis.

Purpose Young adults have the highest cumulative incidence of COVID-19 infection in the country. Using March 2021 Household Pulse Survey data, an ongoing, cross-sectional nationally representative survey, we examined U.S. young adult intention to accept COVID-19 vaccines. Methods Young adult (ages 18–25 years) Household Pulse Survey participants were queried on intention to receive a COVID-19 vaccine and related perspectives (N = 5,082). Results Most unvaccinated respondents (76%) indicated an intention to become vaccinated. The most frequently cited reasons for potentially rejecting vaccination included desire to wait and see if the vaccine is safe (56%); concerns over side effects (53%); and believing others are in greater need of the vaccine (44%). Conclusions With 24% of young adults hesitant to accept a COVID-19 vaccine, public health interventions should target reasons for hesitancy, address concerns about safety and side effects, and underscore the importance of vaccinations for this population.

This paper describes the design and implementation of Black Lion, a purely software-based, distributed environment for integrated testing of independent spacecraft mission models. The Black Lion si...

A range of upcoming missions propose to rendezvous in high Earth orbits, including the geostationary orbit region. This region is known to periodically experience high levels of electrostatic charg...

Background Little is known about the long-term reproductive effects of pelvic infection when a levonorgestrel-releasing intrauterine device (LNG-IUD) is in situ. Society guidelines do not recommend removing an LNG-IUD during pelvic infection. Case A 37-year-old woman presented with primary infertility, and the only contributing factor was intrauterine adhesions in the shape of an IUD. She was known to previously have an LNG-IUD and was treated for asymptomatic chlamydia infection while the IUD was in place. After lysis of adhesions, she successfully conceived spontaneously. Conclusion Data on long-term reproductive effects of pelvic infection with an LNG-IUD in situ are not available, and there may be consequences affecting the intrauterine milieu requiring further studies and potential counseling.

Object The conception of individual patient-adjusted treatment strategies is constantly emerging in the field of neuro-oncology. Systemic laboratory markers may allow insights into individual needs and estimated treatment benefit at an earliest possible stage. Therefore, the present study was aimed at analyzing the prognostic significance of preoperative routine laboratory values in patients with newly-diagnosed glioblastoma. Methods Between 2014 and 2019, 257 patients were surgically treated for newly-diagnosed glioblastoma at the Neuro-Oncology Center of the University Hospital Bonn. Preoperative routine laboratory values including red blood cell distribution width (RDW) and platelet count were reviewed. RDW to platelet count ratio (RPR) was calculated and correlated to overall survival (OS) rates. Results Median preoperative RPR was 0.053 (IQR 0.044–0.062). The receiver operating characteristic (ROC) curve indicated an optimal cut-off value for RPR to be 0.05 (AUC 0.62; p = 0.002, 95% CI 0.544–0.685). 101 patients (39%) presented with a preoperative RPR Conclusions The present study suggests the RPR to constitute a novel prognostic inflammatory marker for glioblastoma patients in the course of preoperative routine laboratory examinations and might contribute to a personalized medicine approach.

The work described in this paper harnesses an open-source astrodynamics engine and visualization to quantify the performance of on-board optical navigation. It introduces the Hough Circles transfor...

Background Ending the global tobacco epidemic is a defining challenge in global health. Timely and comprehensive estimates of the prevalence of smoking tobacco use and attributable disease burden are needed to guide tobacco control efforts nationally and globally. Methods We estimated the prevalence of smoking tobacco use and attributable disease burden for 204 countries and territories, by age and sex, from 1990 to 2019 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study. We modelled multiple smoking-related indicators from 3625 nationally representative surveys. We completed systematic reviews and did Bayesian meta-regressions for 36 causally linked health outcomes to estimate non-linear dose-response risk curves for current and former smokers. We used a direct estimation approach to estimate attributable burden, providing more comprehensive estimates of the health effects of smoking than previously available. Findings Globally in 2019, 1·14 billion (95% uncertainty interval 1·13–1·16) individuals were current smokers, who consumed 7·41 trillion (7·11–7·74) cigarette-equivalents of tobacco in 2019. Although prevalence of smoking had decreased significantly since 1990 among both males (27·5% [26·5–28·5] reduction) and females (37·7% [35·4–39·9] reduction) aged 15 years and older, population growth has led to a significant increase in the total number of smokers from 0·99 billion (0·98–1·00) in 1990. Globally in 2019, smoking tobacco use accounted for 7·69 million (7·16–8·20) deaths and 200 million (185–214) disability-adjusted life-years, and was the leading risk factor for death among males (20·2% [19·3–21·1] of male deaths). 6·68 million [86·9%] of 7·69 million deaths attributable to smoking tobacco use were among current smokers. Interpretation In the absence of intervention, the annual toll of 7·69 million deaths and 200 million disability-adjusted life-years attributable to smoking will increase over the coming decades. Substantial progress in reducing the prevalence of smoking tobacco use has been observed in countries from all regions and at all stages of development, but a large implementation gap remains for tobacco control. Countries have a clear and urgent opportunity to pass strong, evidence-based policies to accelerate reductions in the prevalence of smoking and reap massive health benefits for their citizens. Funding Bloomberg Philanthropies and the Bill & Melinda Gates Foundation.

Background: Pierre Robin sequence (PRS) is a rare congenital anomaly. Respiratory disorders and feeding difficulties represent the main burden. Objective: The aim of this study was to investigate the epidemiology of PRS using a cohort of cases from EUROCAT, the European network of population-based registries of congenital anomalies. Methods: We analysed cases of PRS born in the period 1998-2017 collected by 29 population-based congenital anomaly registries in 17 different countries. We calculated prevalence estimates, prenatal detection rate, survival up to 1 week, and proportions of associated anomalies. The effect of maternal age was tested using a Poisson regression model. Results: Out of 11 669 155 surveyed births, a total of 1294 cases of PRS were identified. The estimate of the overall prevalence was 12.0 per 100 000 births (95% CI 9.9, 14.5). There was a total of 882 (68.2%) isolated cases, and the prevalence was 7.8 per 100 000 births (95% CI 6.7, 9.2). A total of 250 cases (19.3%) were associated with other structural congenital anomalies, 77 cases (6.0%) were associated with chromosomal anomalies and 77 (6.0%) with genetic syndromes. The prenatal detection rate in isolated cases was 12.0% (95% CI 9.8, 14.5) and increased to 16.0% (95% CI 12.7, 19.7) in the sub-period 2008-2017. The prevalence rate ratio of non-chromosomal cases with maternal age ≥35 was higher than in cases with maternal age

This paper introduces a linear model for spacecraft formation dynamics subject to attitude-dependent solar radiation pressure (SRP) disturbance, with the SRP model accounting for both absorption and specular/diffuse reflection. Spacecraft attitude is represented in modified Rodriguez parameters (MRPs), which also parameterize the orientation of individual facets for a spacecraft with fixed geometry. Compared to earlier work, this model incorporates analytic approximation of the SRP-perturbed chief orbit behavior in a manner enabling its use in applications with infrequent guidance updates. Control examples are shown for single-plate representations of hypothetical spacecraft with generally realistic optical parameters. The results demonstrate the validity of the model and the feasibility of SRP-based formation and rendezvous control in orbits around small bodies and in high orbits around the Earth such as the GEO belt.

This paper explores methods for approximating and analyzing the dynamics of highly perturbed spacecraft formations with an emphasis on computationally efficient approaches. This facilitates on-board computation or rapid preliminary mission design analysis. Perturbed formation dynamics are often approximated as linear time-varying (LTV) systems, for which Floquet theory can be used to analyze the degree of system instability. Furthermore, the angular momentum of the relative orbital state can be computed with the approximate dynamics to provide additional insight. A general methodology is developed first and then applied to the problem of unstable formation dynamics in asteroid orbits. Here the dominant perturbative effects due to low-order gravitational harmonics and solar radiation pressure are modeled. Numerical simulations validate the approach and illustrate the approximation accuracy achieved.

Das Risiko der Abstosung und des Transplantatversagens nach Hochrisikokeratoplastik steigt mit Zunahme der kornealen Neovaskularisation. Die medikamentose und physikalische Regression der kornealen Neovaskularisation vor Keratoplastik bietet moglicherweise das Potenzial, das Risiko einer Abstosung nach anschliesender Hochrisikokeratoplastik zu reduzieren. Die vorliegende Arbeit gibt eine Literaturubersicht hinsichtlich der Prakonditionierung von vaskularisierten Hochrisikoaugen mittels Feinnadeldiathermie und kornealem Crosslinking vor Hochrisikokeratoplastik („lymphangioregressive Prakonditionierung“). Es erfolgen eine Literaturrecherche via PubMed sowie eine Zusammenfassung eigener Daten. Tierexperimentelle Studien zeigen, dass sowohl die Feinnadeldiathermie als auch das korneale Crosslinking zu einer Regression der kornealen Neovaskularisation fuhren und das Transplantatuberleben nach anschliesender Hochrisikokeratoplastik verlangern. Untersuchungen aus unserem Institut geben daruber hinaus erste Hinweise, dass beide Verfahren auch in der klinischen Praxis zur Reduktion der kornealen Neovaskularisation fuhren und damit potenziell das Abstosungsrisiko reduzieren. Die Feinnadeldiathermie und das korneale Crosslinking bieten effektive Therapieansatze zur angioregressiven Behandlung und scheinen das Transplantatuberleben nach Hochrisikokeratoplastik zu verlangern. Groser angelegte prospektive und kontrollierte klinische Studien sind notwendig, um diese vielversprechenden Therapieansatze weitergehend zu untersuchen.

Purpose: The CeTeG/NOA-09 phase III trial demonstrated a significant survival benefit of lomustine–temozolomide chemoradiation in patients with newly diagnosed glioblastoma with methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter. Following lomustine–temozolomide chemoradiation, late and prolonged pseudoprogression may occur. We here evaluated the value of amino acid PET using O-(2-[18F]fluoroethyl)-l-tyrosine (FET) for differentiating pseudoprogression from tumor progression. Experimental Design: We retrospectively identified patients (i) who were treated off-study according to the CeTeG/NOA-09 protocol, (ii) had equivocal MRI findings after radiotherapy, and (iii) underwent additional FET-PET imaging for diagnostic evaluation (number of scans, 1–3). Maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) and dynamic FET uptake parameters (e.g., time-to-peak) were calculated. In patients with more than one FET-PET scan, relative changes of TBR values were evaluated, that is, an increase or decrease of >10% compared with the reference scan was considered as tumor progression or pseudoprogression. Diagnostic performances were evaluated using ROC curve analyses and Fisher exact test. Diagnoses were confirmed histologically or clinicoradiologically. Results: We identified 23 patients with 32 FET-PET scans. Within 5–25 weeks after radiotherapy (median time, 9 weeks), pseudoprogression occurred in 11 patients (48%). The parameter TBRmean calculated from the FET-PET performed 10 ± 7 days after the equivocal MRI showed the highest accuracy (87%) to identify pseudoprogression (threshold, Conclusions: The data suggest that FET-PET parameters are of significant clinical value to diagnose pseudoprogression related to lomustine–temozolomide chemoradiation.

A method for the fast computation of spacecraft force and torque due to solar radiation pressure (SRP) is presented. A faceted model is employed that tracks which elements of a time-varying geometr...

Immune checkpoint inhibitors are approved for a variety of indications for locally advanced and metastatic non-small cell lung cancer (NSCLC), and trials are ongoing in the early-stage setting. There is an unmet need to understand which patients may derive benefit from immunotherapies and how to harness combined modality therapies to improve overall response rates and durability. Here, we review studies from the bench-to-bedside to examine the role of radiation therapy (RT) on the tumor immune microenvironment in NSCLC with an eye toward augmenting antitumor immunity. Together, these data provide a foundation for developing future clinical trials harnessing RT to augment antitumor immunity and highlight the need for correlative translational studies to directly characterize the impact of RT on the human NSCLC tumor immune microenvironment.

This paper investigates different strategies for end-to-end flight software development that support having both desktop and embedded environments while minimizing the existing gap between them, in...

Bei schwerstbeeintrachtigten und vaskularisierten Hochrisikoaugen stellt die Versorgung mittels Boston-Keratoprothese die oftmals letzte Therapieoption dar. Die Transparenz der Optik wird hier nicht durch endotheliale Abstosungsreaktionen beeintrachtigt. In diesem Ubersichtsbeitrag werden relevante Literatur sowie eigene Daten und Erfahrungen zur Versorgung von Hochrisikoaugen mit der Boston-Keratoprothese diskutiert. Die relevanten Komplikationen sowie das postoperative Management werden erortert. In mehr als 60 % der Hochrisikoaugen kann durch eine Keratoprothesenversorgung langfristig ein Visusanstieg erreicht werden. Keratoprothesenretentionswerte schwanken stark, nach 5 Jahren liegen diese im Mittel bei 75 %. Die haufigsten postoperativen Komplikationen umfassen die Ausbildung einer retroprothetischen Membran und das Auftreten von Keratolysen in jeweils bis zu 50 %. Bereits praoperativ leiden mehr als 70 % der Augen an einem (Sekundar‑)Glaukom, sodass ein glaukomchirurgischer Eingriff simultan in mindestens 20 % der Falle erfolgt und im postoperativen Verlauf in bis zu 31 % ein weiterer Eingriff erforderlich wird. Vitreoretinale Komplikationen umfassen insbesondere die sterile Vitritis und die infektiose Endophthalmitis, aber auch die persistierende Bulbushypotonie ist bei einem Drittel der Patienten beschrieben. Die Boston-Keratoprothese kommt bei sehr schlechter Prognose fur einen konventionellen Hornhautersatz infrage. Postoperative Komplikationen sind haufig, sodass dem postoperativen Management eine wichtige Rolle zukommt. Fur vaskularisierte Hochrisikoaugen ist sie jedoch oftmals die einzige verbliebene Option zur Visusrehabilitation.

BACKGROUND Specific allergy sensitization pattern, using "component-resolved diagnosis" (CRD), is a central component of allergy and asthma in childhood. Besides this, allergic asthma has been characterized by a Th2-shifted endotype with elevation of classical Th2 cytokines. Recently, other endotypes with distinct mechanisms focusing on cytokine regulation evolved, yet those pathways are still not well understood. OBJECTIVE (a) To define reproducible immunological endotypes using cytokine expression in an asthma cohort and (b) to characterize their sensitization profile and clinical phenotype. METHODS Supernatants from PBMCs of 234 children (median age 10 years) of an asthma cohort were analysed for cytokine expressions. The children were split into a training (n = 49) and validation (n = 185) group. The training group was used to identify immunological endotypes by clustering cytokine expressions, which were then assessed regarding clinical characteristics and specific IgE of recombinant allergen components. Next, our findings were validated in the validation group. RESULTS We identified novel endotypes based on primarily unstimulated cytokine expression. One endotype showed an IFN-γ/Interleukin (IL)-17/IL-5 predominance, a different sensitization pattern (high in birch/apple; p

AimsDetection of one segmentally sclerosed glomerulus (SSG) identifies patients with focal segmental glomerulosclerosis (FSGS) but rare SSGs may be missed in kidney biopsies. It is unknown whether alterations of unaffected glomeruli in patients with infrequent SSG can be detected by quantitative morphometrics.MethodsWe determined SSG frequency and obtained quantitative morphometrics in glomeruli without a pathologic phenotype in large kidney sections of non-involved kidney tissue from 137 patients undergoing total nephrectomy. We used multivariate modelling to identify morphometrics independently associated with increasing frequency of SSG and Receiver Operator Curve (ROC) analysis to determine the ability of quantitative morphometrics to identify patients with FSGS. We used the geometric distribution to estimate the sensitivity and specificity of a needle biopsy to identify patients with FSGS.ResultsIn seventy-one patients (51.8%), at least one SSG was observed, and of those, 39 (54.9%) had an SSG lesion in less than 2% of all glomeruli (mean of 249 glomeruli per specimen). Increasing percent of SSG was independently associated with decreasing podocyte density and increasing mesangial index in multivariate modelling. For infrequent SSG lesions (ConclusionsMore than half of patients had FSGS, although 30% had infrequent SSG. Quantitative morphometrics in glomeruli without pathology, such as podocyte density and mesangial index, identified patients with infrequent SSG and may serve as clinical markers to identify patients with FSGS.

COVID-19 morbidity and mortality are increased in patients with diabetes and kidney disease via unknown mechanisms. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for entry into host cells. Since ACE2 is a susceptibility factor for infection, we investigated how diabetic kidney disease and medications alter ACE2 receptor expression in kidneys. Single cell RNA profiling of healthy living donor and kidney biopsies from patients with diabetic kidney disease revealed ACE2 expression primarily in proximal tubular epithelial cells. This cell specific localization was confirmed by in situ hybridization. ACE2 expression levels were unaltered by exposures to renin angiotensin aldosterone system inhibitors in diabetic kidney disease. Bayesian integrative analysis of a large compendium of public-omics datasets identified molecular network modules induced in ACE2-expressing proximal tubular epithelial cells in diabetic kidney disease (searchable at hb.flatironinstitute.org/covid-kidney) that were linked to viral entry, immune activation, endomembrane reorganization, and RNA processing. The diabetic kidney disease ACE2-positive proximal tubular epithelial cell module overlapped with expression patterns seen in SARS-CoV-2 infected cells. Similar cellular programs were seen in ACE2-positive proximal tubular epithelial cells obtained from urine samples of 13hospitalized patients with COVID-19, suggesting a consistent ACE2-coregulated proximal tubular epithelial cell expression program that may interact with the SARS-CoV-2 infection processes. Thus SARS-CoV-2 receptor networks can seed further research into risk stratification and therapeutic strategies for COVID-19 related kidney damage., Graphical abstract

The CeTeG/NOA-09 trial showed a survival benefit for combined CCNU/TMZ therapy in MGMT-promoter-methylated glioblastoma patients (quantitative methylation-specific PCR [qMSP] ratio > 2). Here, we report on the prognostic value of the MGMT promoter methylation ratio determined by qMSP and evaluate the concordance of MGMT methylation results obtained by qMSP, pyrosequencing (PSQ) or DNA methylation arrays (MGMT-STP27). A potential association of qMSP ratio with survival was analyzed in the CeTeG/NOA-09 trial population (n = 129; log-rank tests, Cox regression analyses). The concordance of MGMT methylation assays (qMSP, PSQ and MGMT-STP27) was evaluated in 76 screened patients. Patients with tumors of qMSP ratio > 4 showed superior survival compared to those with ratios 2-4 (P = .0251, log-rank test). In multivariate analysis, the qMSP ratio was not prognostic across the study cohort (hazard ratio [HR] = 0.88; 95% CI: 0.72-1.08). With different cutoffs for qMSP ratio (4, 9, 12 or 25), the CCNU/TMZ benefit tended to be larger in subgroups with lower ratios (eg, for cutoff 9: HR 0.32 for lower subgroup, 0.73 for higher subgroup). The concordance rates with qMSP were 94.4% (PSQ) and 90.2% (MGMT-STP27). Discordant results were restricted to tumors with qMSP ratios ≤4 and PSQ mean methylation rate ≤25%. Despite a shorter survival in MGMT-promoter-methylated patients with lower methylation according to qMSP, these patients had a benefit from combined CCNU/TMZ therapy, which even tended to be stronger than in patients with higher methylation rates. With acceptable concordance rates, decisions on CCNU/TMZ therapy may also be based on PSQ or MGMT-STP27.

Purpose Conventionally fractionated, post-operative radiotherapy (cPORT; 50 Gy in 25 fractions) is considered for patients with Merkel cell carcinoma (MCC) to improve locoregional control. However, cPORT is associated with acute toxicity, especially in the head and neck (H&N) region, and requires daily treatments over several weeks. We previously reported high rates of durable local control with minimal toxicity using 8 Gy single-fraction radiation therapy (SFRT) in the metastatic setting. We report early results on a cohort of patients with localized H&N MCC, who received post operative SFRT if a cPORT regimen was not feasible. Methods Twelve patients with localized MCC of the H&N (clinical/pathologic stages: I-II) and no prior RT to the region were identified from an IRB-approved prospective registry who underwent surgical resection followed by post operative SFRT. Time-to-event was calculated starting from the date of resection prior to SFRT. The cumulative incidence of in-field locoregional recurrences and out-of-field recurrences was estimated with death as a competing risk. Results Twelve H&N MCC patients were identified with clinical/pathologic stages I-II H&N MCC. Median age at diagnosis was 81 years (58-96); 25% had immunosuppression. At a median follow-up of 19 months (range: 8-34), there were no in-field locoregional recurrences. A single out-of-field regional recurrence was observed, which was successfully salvaged. There were no MCC specific-deaths. No radiation-associated toxicities greater than grade 1 (CTCAE v5) were observed. Conclusions Preliminary data suggest that SFRT could offer a potential alternative to cPORT to treat the primary site for localized H&N MCC, particularly in elderly or frail patients, with promising in-field local control and minimal toxicity. Further data with validation in larger cohorts is needed to confirm the sustained safety and efficacy of post operative SFRT., Merkel cell carcinoma (MCC) is often treated with excision followed by conventional fractionated radiotherapy for localized disease. Single fraction radiation therapy (SFRT) has been shown to be effective for treating patients with metastatic MCC. This study presents early results for patients with MCC of the head and neck treated with 8 Gy SFRT to the post operative bed following surgery.

ZusammenfassungDieser Beitrag beinhaltet eine Übersicht über die Epidemiologie, die Risikofaktoren und das klinische Bild sowie die Diagnostik der rhegmatogenen (rissbedingten) Netzhautablösung. Diese ist von einer Retinoschisis sowie den traktiven und exsudativen Formen der Netzhautablösung hinsichtlich ihrer Häufigkeit, den Risikofaktoren, ihrer Entstehung und dem klinischen Bild zu unterscheiden.

Ziel ist die Bergung einer in den Glaskorperraum luxierten Intraokularlinse (IOL) mit sekundarer, retroiridal platzierter inverser Irisklauenlinsenimplantation uber die Pars plana ohne Notwendigkeit des Erweiterns des kornealen Tunnelschnittes. Ziele der Operationstechnik sind die Vermeidung eines kornealen Astigmatismus nach sekundarer Linsenimplantation, eine schnellere Visusrehabilitation und Reduktion invasiver Manover in der Vorderkammer. Indikation ist die In-the-bag-Luxation einer nicht refixierbaren Hinterkammerlinse in den Glaskorperraum bei Zonulopathie. Ausgedehnte Irisstromadefekte, Iritis, Skleromalazie und ischamische Retinopathien gelten als Kontraindikationen. Die Technik besteht in der Bergung der IOL im Rahmen einer standardisierten konventionellen Vitrektomie (20 Gauge) uber eine erweiterte Sklerotomie und anschliesend Implantation einer Irisklauenlinse invers, retroiridal ebenfalls uber die Pars plana. Das Operationsvideo steht online zur Verfugung. Es erfolgt eine 3‑wochige Lokaltherapie mit Steroiden und antimikrobiellen Substanzen lokal, ggf. Tunnelfadenzug 14 Tage nach dem Eingriff. Die Implantation einer retroiridalen Irisklauenlinse ist ein etabliertes Verfahren. Das Einbringen uber die Pars plana in der vorgestellten Form ist eine Erstbeschreibung.

Aim of our prospective pilot study was to assess the feasibility of computed tomography (CT) to visualize the normal parathyroid gland in dogs and provide a description of its CT appearance.A total of 25 dogs, which received CT imaging including the neck region for diseases unrelated to the thyroid or parathyroid glands, were enrolled. Inclusion criteria were a normal physical examination, an unremarkable complete blood count and serum chemistry profile. Pre and post contrast CT images were acquired using a 16-slice helical scanner with an 18 cm field of view, 1 mm slice thickness and a 512 × 512 matrix. Post contrast images were obtained 30-45 seconds following contrast medium injection (early venous phase). CT-images were independently reviewed by 2 radiologists. Visibility of the parathyroid gland was recorded and inter-observer agreement was calculated. For all visualized parathyroid glands the following parameters were assessed: size, density in Hounsfield units (HU) on pre and post contrast images, density of the thyroid gland and border definition (excellent, moderate, poor).Only 20 respectively 25 parathyroid glands could be visualized by the 2 observers. The number did not vary between pre and post contrast images. The inter-observer agreement for the identification was fair (κ = 0.40). Length, width and height (mean ± standard deviation) of the parathyroid gland were 4.2 × 2.5 × 2.9 mm ± 1.3 × 0.8 × 1.0 mm. The density was 39.7 ± 20.6 HU on pre contrast images and 103.1 ± 47.1 HU on post contrast images, thus the organ was hypoattenuating compared to the thyroid gland on pre (166.7 ± 34.3 HU) and post contrast (234.0 ± 60.1 HU) images.This study offers the first description of the CT appearance of the presumed normal canine parathyroid gland. However, the overall visibility was poor.Despite the overall poor visibility of the parathyroid gland it was occasionally visible and its CT dimensions were larger as described for ultrasound in this group of dogs, which showed no clinical signs of hyperparathyroidism. Thus, visibility of the parathyroid gland on CT may not necessarily imply parathyroid disease. However, further research is necessary.Ziel dieser prospektiven Pilotstudie war zu beurteilen, ob die physiologische Glandula parathyroidea beim Hund computertomografisch dargestellt werden kann, und eine Beschreibung ihres CT-Erscheinungsbildes zu geben.In die Studie wurden 25 Hunde aufgenommen, bei denen aufgrund von Erkrankungen im Halsbereich ohne Bezug zu Schild- oder Nebenschilddrüse ein CT-Scan erfolgte. Einschlusskriterium waren unauffällige Befunde bei der allgemeinen klinischen Untersuchung und der Blutuntersuchung (Blutbild und blutchemische Analyse). CT-Bilder vor und nach Kontrastmittelapplikation (30–45 Sekunden nach der Kontrastmittelinjektion, frühe venöse Phase) wurden mit einem 16-Schichten-Spiral-CT unter Verwendung eines Field of View von 18 cm, einer Schichtdicke von 1 mm und einer Matrix von 512 × 512 angefertigt. Zwei Radiologen begutachteten die CT-Aufnahmen unabhängig voneinander. Die Sichtbarkeit der Parathyreoidea wurde erfasst und die Interobserver-Reliabilität ermittelt. Bei den darstellbaren Nebenschilddrüsen wurden folgende Parameter bestimmt: Größe, Dichte (in Hounsfield Units [HU], vor und nach Kontrastmittelgabe), Dichte der Schilddrüse, Abgrenzung (exzellent, mäßig, schlecht).Nur 20 bzw. 25 Nebenschilddrüsen waren durch die beiden Untersucher erkennbar. Die Anzahl differierte zwischen Nativaufnahmen und Bildern nach Kontrastmittelgabe nicht. Die Interobserver-Reliabilität hinsichtlich der Erkennbarkeit war moderat (κ = 0,40). Für Länge, Breite und Höhe der Nebenschilddrüsen (Mittelwert ± Standardabweichung) ergaben sich 4,2 × 2,5 × 2,9 mm ± 1,3 × 0,8 × 1,0 mm. Die Dichte betrug 39,7 ± 20,6 HU vor und 103,1 ± 47,1 HU nach Kontrastmittelgabe. Damit stellten sich die Nebenschilddrüsen im Vergleich zur Schilddrüse (vor und nach Kontrastmittelgabe 166,7 ± 34,3 HU bzw. 234,0 ± 60,1 HU) hypoattenuierend dar.Diese Studie liefert die erste Beschreibung des CT-Erscheinungsbilds der angenommen physiologischen Nebenschilddrüse beim Hund. Die Sichtbarkeit des Organs war jedoch schlecht.Trotz der schlechten Visualisierung der Nebenschilddrüse im CT ist sie gelegentlich wahrnehmbar. Die ermittelten Dimensionen waren teilweise größer als bisher für sonografische Darstellung beschrieben, ohne dass die untersuchten Hunde erkennbare Symptome eines Hyperparathyreodismus aufwiesen. Eine computertomografisch sichtbare Nebenschilddrüse impliziert daher möglicherweise nicht unbedingt eine Erkrankung. Weitere Studien dazu sind notwendig.

Background: Ventricular assist device (VAD) patients are at high risk for morbidities and mortality. One potentially beneficial component of the Joint Commission VAD Certification process is the requirement that individual VAD programs select 4 performance measures to improve and optimize patients’ clinical outcomes. Problem Statement: Review of patient data after our program’s first certification visit in 2008 showed that, compared to national recommendations and published reports, our patients had suboptimal outcomes in 4 areas after device implantation: length of hospital stay, receipt of early (Methods: Plan-Do-Study-Act processes were implemented to shorten length of stay, increase patient receipt of early physical therapy, decrease driveline infection incidence, and improve nutritional status. With 2008 as our baseline, we deployed interventions for each outcome area across 2009 to 2017. Performance improvement activities included staff, patient, and family didactic, one-on-one, and hands-on education; procedural changes; and outcomes monitoring with feedback to staff on progress. Descriptive and inferential statistics were examined to document change in the outcomes. Outcomes: Across the performance improvement period, length of stay decreased from 40 to 23 days; physical therapy consults increased from 87% to 100% of patients; 1-year driveline infection incidence went from 38% to 23.5%; and the percentage of patients with prealbumin within the normal range increased from 84% to 90%. Implications: Performance improvement interventions may enhance ventricular assist device patient outcomes. Interventions’ sustainability should be evaluated to ensure that gains are not lost over time.

Eplets are functional units of structural epitopes on donor HLA, potentially recognized by complementarity-determining regions of the paratope of the recipients' B-cell receptors or antibodies (Ab). Their individual immunogenicity is poorly described, yet this feature would be of clinical importance for pretransplant risk assessment. The aim of this study was to determine the relative immunogenicity of HLA class I eplets in the pregnancy setting, where mismatched eplets are present on paternal HLA antigens of the unborn child. One hundred fifty-nine predominantly Caucasian mothers giving birth at the University Hospital Basel and their first newborns were HLA-typed at high-resolution by next-generation sequencing (NGS) (NGSgo Workflow and NGSengine from GenDx; sequencing with a Miseq from Illumina) and eplets were determined using HLAMatchmaker. HLA class I specific IgG Ab was assessed in maternal sera drawn immediately after full-term delivery, by OneLambda LABScreen single antigen ibeads. The Ab profile was subsequently evaluated for eplet-associated patterns. All 72 currently Ab-verified HLA class I eplets were examined for their immunogenicity according to the frequency of child-specific HLA Ab (CSA) directed against their structures. Four hundred twelve of 477 (86.4%) paternal HLA-A, -B or -C alleles were mismatched. CSA were present in 46 mothers (28.9%), directed against 80 (19.4%) of these mismatches. The 10 most immunogenic eplets were 62GK, 145KHA, 144TKH, 62GE, 107W, 80I, 82LR, 41T, 127K, 45KE with immunogenicity rates between 45.8% and 27.3%. This pregnancy study also identified five non-reactive eplets: 62RR, 76ESN, 80TLR, 156DA, 163RW. Based on our results, immunogenic hot and cold spots on the surface of HLA class I molecules were localized and visualized on 3D models. This study strengthens the presumption that different eplets represent different immunogenic potentials. Validation of these results in the clinical transplant setting is an essential next step in identifying those eplets representing a particularly high-risk potential.

The Basilisk astrodynamics framework is a spacecraft simulation tool developed with an aim of strict modular separation and decoupling of modeling concerns in regard to coupled spacecraft dynamics,...

Fruhkindliches Giemen, im Englischen „wheeze“, ist ein sehr haufiges Symptom im Kleinkind- und Vorschulalter, das oft zu Arzt- und auch Krankenhausvorstellungen fuhrt und die betroffenen Familien stark belasten kann. Die Aufgaben des Kinderarztes in der Begleitung der betroffenen Kinder und ihrer Familien sind vielfaltig. Angefangen mit der sorgfaltigen Anamnese, um herauszuarbeiten, ob tatsachlich ein Giemen vorliegt oder andere Atemgerausche sowie Anhaltspunkte fur spezifische Grunderkrankungen zu identifizieren, die ebenfalls mit einem Giemen einhergehen. Die weitere Diagnostik sollte auch orientierende allergologische Tests auf spezifische Sensibilisierungen beinhalten, um das Risiko der Asthmaentwicklung einzugrenzen. Eine positive Begleitung auf Basis der grundsatzlich guten Prognose, unterstutzt durch Elemente der Patientenschulung, kann hilfreich sein, damit medikamentose Therapien nicht unkritisch gemas den Leitlinien des Asthma bronchiale erfolgen, da die Evidenz fur viele medikamentose Interventionen im Vorschulalter deutlich geringer ist als im Schulalter und bei Erwachsenen. Eine gute Zusammenarbeit von Kinderarzten und Wissenschaftlern ist unabdingbar, um praxisorientierte Risikofaktoren zu identifizieren, die den Krankheitsverlauf besser vorhersagen konnen sowie Interventionsmoglichkeiten zu entwickeln und zu uberprufen.

SummaryHen Harrier Circus cyaneus and Short-eared Owl Asio flammeus are open-country birds of prey with overlapping distributions. Although both species face similar conservation threats across their ranges, work to date has largely been undertaken at a national scale with few attempts to collate and assess factors relevant to their conservation at an international scale. Here we use an expert knowledge approach to evaluate the impact of conservation threats and the effectiveness of conservation strategies for each species across Europe. We report results of responses to a questionnaire from 23 Hen Harrier experts from nine countries and 12 Short-eared Owl experts from six countries. The majority of responses for both species reported declines in breeding numbers. The perceived impact of threats was broadly similar for both species: ecological factors (predation, extreme weather and prey availability), changes in land use (habitat loss and agricultural intensification) and indirect persecution (accidental nest destruction) were considered to be the greatest threats to breeding Hen Harrier and Short-eared Owl. Short-eared Owl experts also highlighted lack of knowledge and difficulties associated with monitoring as a major conservation challenge. Despite broad-scale similarities, geographical variation was also apparent in the perceived importance of conservation threats, with some threats (such as direct persecution, large-scale afforestation or habitat degradation) requiring country-specific actions. Implementation of different conservation strategies also varied between countries, with the designation of protected areas reported as the most widespread conservation strategy adopted, followed by species and habitat management. However, protected areas (including species-specific protected areas) were perceived to be less effective than active management of species and habitats. These findings highlight the overlap between the conservation requirements of these two species, and the need for collaborative international research and conservation approaches that prioritise pro-active conservation strategies subject to continued assessment and with specific conservation goals.

The term “creative space” describes a relatively recent phenomenon of innovative workplace design. Such creative workspaces are becoming popular in industry and academia. However, the impact of specific spatial design decisions on creativity and innovation is not yet fully understood. This paper provides an overview of state-of-the-art research on creative work and learning environments. We conducted a systematic literature search within the Scopus database and identified a total of 73 relevant sources discussing creative spaces within academic, practice, and other innovation environments. Among the included sources are 51 academic publications and 22 sources from company research and illustrative coffee-table books. We analyzed the sources using three lenses of interest: (1) the types of theoretical and practical contributions that are provided, (2) the spatial characteristics that are suggested to be beneficial for creativity and innovation, and (3) the discussed potential of new technologies for designing or researching creative spaces. The results provide in-depth insight into the current state of research on the topic of creative spaces. Practitioners, educators, and researchers can use the presented overview to investigate the possible impact of creative workspace design and identify research gaps that can be filled by conducting further research in the field.

Der haufigen Begleiterscheinung einer Makulopathie bei Grubenpapille scheint ein pathogenetisch nicht abschliesend ergrundeter Flussigkeitsaustausch zwischen Papille und Makula zugrunde zu liegen. Ein chirurgisches Vorgehen durch Vitrektomie mit Erzeugung einer Barriere zwischen Makula und Grubenpapille beispielsweise mittels Endolaser oder Skleraflap ist moglich. Daneben stellt die hier im Detail dargestellte partielle Retinafensterung eine Alternative dar, durch die Flussigkeit von der Grubenpapille in den Glaskorperraum geleitet wird. Die vollstandige Resorption der sub- und intraretinalen Flussigkeit kann innerhalb des ersten postoperativen Jahres erwartet werden.

BACKGROUND Proliferative vitreoretinopathy (PVR) is one of the most important complications following vitreoretinal surgery. So far, surgical strategies have been the gold standard in treatment. Pharmacological approaches for prevention and treatment of PVR are under clinical investigation and intervene in different phases of the PVR cascade. METHODS The relevant literature as well as own data and experience with PVR are discussed in this review article. The most important aspects of pharmacological approaches for PVR prophylaxis and treatment are explained. RESULTS A prophylactic use of systemic prednisone administration as an anti-inflammatory substance showed contradictory results, while there was no additional benefit for intravitreal triamcinolone. Orally administered isotretinoin also seems to be able to minimize the formation of PVR after retinal reattachment surgery, whereas there was no improvement in the success rate in established PVR. Cell proliferation inhibitors have already been extensively studied. The combined intravitreal prophylactic approach of 5‑fluorouracil and low molecular weight heparin was recently further investigated in a multicenter, placebo-controlled study and showed a positive effect in some studies. New preclinical and experimental approaches include the inhibition of growth factors, modulation of integrin activity and the induction of apoptosis. CONCLUSION Most clinical studies dealt with an anti-inflammatory or antiproliferative approach. So far, no pharmacological substance has been established for the treatment of PVR but there are promising approaches for prophylaxis.