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Early-career faculty (ECF) are faced with maintaining excellence in teaching and research for tenure. However, many enter academia with little or no teaching experience. Madison Teaching and Learni...

Amyloidosis is a localized or systemic process where extracellular insoluble plasma protein fibers are deposited into tissues. Localized amyloidosis is rare and curable by surgical resection. While the head and neck region represents 19% of localized amyloidosis cases, only one other case of bilateral involvement of the pharyngeal tonsils has been published in the international literature. We report a case of asymptomatic amyloidosis isolated to the bilateral palatine tonsils and a cervical lymph node in a 59-year-old male. Systemic amyloidosis was ruled out through multidisciplinary consultation, and resection of the masses was performed. This represents the second reported case of bilateral tonsillar amyloidosis.

Background: Treatment resistance of glioblastoma multiforme to chemo- and radiotherapy remains a challenge yet to overcome. In particular, the O6-methylguanine-DNA-methyltransferase (MGMT) promoter unmethylated patients have only little benefit from chemotherapy treatment using temozolomide since MGMT counteracts its therapeutic efficacy. Therefore, new treatment options in radiotherapy need to be developed to inhibit MGMT and increase radiotherapy response. Methods: Lomeguatrib, a highly specific MGMT inhibitor, was used to inactivate MGMT protein in vitro. Radiosensitivity of established human glioblastoma multiforme cell lines in combination with lomeguatrib was investigated using the clonogenic survival assay. Inhibition of MGMT was analyzed using Western Blot. Cell cycle distribution and apoptosis were investigated to determine the effects of lomeguatrib alone as well as in combination with ionizing radiation. Results: Lomeguatrib significantly decreased MGMT protein and reduced radiation-induced G2/M arrest. A radiosensitizing effect of lomeguatrib was observed when administered at 1 µM and increased radioresistance at 20 µM. Conclusion: Low concentrations of lomeguatrib elicit radiosensitization, while high concentrations mediate a radioprotective effect.

Tumor cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface, where it can be recognized by pre‐activated NK cells. In our retrospective study the expression of Hsp70 was determined in relation to tumor‐infiltrating CD56+ NK cells in formalin‐fixed paraffin embedded (FFPE) tumor specimens of patients with SCCHN (N = 145) as potential indicators for survival and disease recurrence. All patients received radical surgery and postoperative cisplatin‐based radiochemotherapy (RCT). In general, Hsp70 expression was stronger, but with variable intensities, in tumor compared to normal tissues. Patients with high Hsp70 expressing tumors (scores 3–4) showed significantly decreased overall survival (OS; p = 0.008), local progression‐free survival (LPFS; p = 0.034) and distant metastases‐free survival (DMFS; p = 0.044), compared to those with low Hsp70 expression (scores 0–2), which remained significant after adjustment for relevant prognostic variables. The adverse prognostic value of a high Hsp70 expression for OS was also observed in patient cohorts with p16‐ (p = 0.001), p53‐ (p = 0.0003) and HPV16 DNA‐negative (p = 0.001) tumors. The absence or low numbers of tumor‐infiltrating CD56+ NK cells also correlated with significantly decreased OS (p = 0.0001), LPFS (p = 0.0009) and DMFS (p = 0.0001). A high Hsp70 expression and low numbers of tumor‐infiltrating NK cells have the highest negative predictive value (p = 0.00004). In summary, a strong Hsp70 expression and low numbers of tumor‐infiltrating NK cells correlate with unfavorable outcome following surgery and RCT in patients with SCCHN, and thus serve as negative prognostic markers., What's new? It's difficult to predict how a patient with squamous‐cell carcinoma of the head and neck (SCCHN) will respond to treatment, because every tumor is different. In this study, the authors identified two pre‐treatment measures that were associated with poor prognosis following surgery and RCT: high levels of staining for a protein called Hsp70 in tumor cells, and low numbers of tumor‐infiltrating NK lymphocytes. These measures may thus serve as useful prognostic biomarkers for predicting the response of SCCHN to therapy.

Background Asymptomatic carotid artery stenosis (ACS) has a low risk of stroke. To achieve an advantage over noninterventional best medical treatment (BMT), carotid endarterectomy (CEA) or carotid artery stenting (CAS) must be performed with the lowest possible risk of stroke. Therefore, an analysis of risk-elevating factors is essential. Grade of ipsilateral and contralateral stenosis as well as plaque morphology are known risk factors in ACS. Methods The randomized, controlled, multicenter SPACE-2 trial had to be stopped prematurely after recruiting 513 patients. 203 patients were randomized to CEA, 197 to CAS, and 113 to BMT. Within one year, risk factors such as grade of stenosis and plaque morphology were analyzed. Results Grade of contralateral stenosis (GCS) was higher in patients with any stroke (50%ECST vs. 20%ECST; p=0.012). Echolucent plaque morphology was associated with any stroke on the day of intervention (OR 5.23; p=0.041). In the periprocedural period, any stroke was correlated with GCS in the CEA group (70%ECST vs. 20%ECST; p=0.026) and with echolucent plaque morphology in the CAS group (6% vs. 1%; p=0.048). In multivariate analysis, occlusion of the contralateral carotid artery (CCO) was associated with risk of any stroke (OR 7.00; p=0.006), without heterogeneity between CEA and CAS. Conclusion In patients with asymptomatic carotid artery stenosis, GCS, CCO, as well as echolucent plaque morphology were associated with a higher risk of cerebrovascular events. The risk of stroke in the periprocedural period was increased by GCS in CEA and by echolucent plaque in CAS. Due to small sample size, results must be interpreted carefully.

Radiotherapy (RT) is an established treatment for patients with primary and recurrent prostate cancer. Herein, the effects of definitive and salvage RT on the composition of lymphocyte subpopulations were investigated in patients with prostate cancer to study potential immune effects. A total of 33 prostate cancer patients were treated with definitive (n = 10) or salvage RT (n = 23) after biochemical relapse. The absolute number of lymphocytes and the distribution of lymphocyte subpopulations were analyzed by multiparameter flow cytometry before RT, at the end of RT, and in the follow-up period. Absolute lymphocyte counts decreased significantly after RT in both patient groups and a significant drop was observed in the percentage of B cells directly after RT from 10.1 ± 1.3 to 6.0 ± 0.7% in patients with definitive RT and from 9.2 ± 0.8 to 5.8 ± 0.7% in patients with salvage RT. In contrast, the percentages of T and natural killer (NK) cells remained unaltered directly after RT in both patient groups. However, 1 year after RT, the percentage of CD3+ T cells was significantly lower in patients with definitive and salvage RT. The percentage of regulatory T cells was slightly upregulated in primary prostate cancer patients after definitive RT, but not after salvage RT. Definitive and salvage RT exert similar effects on the composition of lymphocyte subpopulations in prostate cancer patients. Total lymphocyte counts are lower in both patient groups compared to healthy controls and further decreased after RT. B cells are more sensitive to definitive and salvage RT than T and NK cells.

The use of different scoring systems for radiation-induced toxicity limits comparability between studies. We examined dose-dependent tissue alterations following hypofractionated X-ray irradiation and evaluated their use as scoring criteria. Four dose fractions (0, 5, 10, 20, 30 Gy/fraction) were applied daily to ear pinnae. Acute effects (ear thickness, erythema, desquamation) were monitored for 92 days after fraction 1. Late effects (chronic inflammation, fibrosis) and the presence of transforming growth factor beta 1 (TGF&beta, 1)-expressing cells were quantified on day 92. The maximum ear thickness displayed a significant positive correlation with fractional dose. Increased ear thickness and erythema occurred simultaneously, followed by desquamation from day 10 onwards. A significant dose-dependency was observed for the severity of erythema, but not for desquamation. After 4 &times, 20 and 4 &times, 30 Gy, inflammation was significantly increased on day 92, whereas fibrosis and the abundance of TGF&beta, 1-expressing cells were only marginally increased after 4 &times, 30 Gy. Ear thickness significantly correlated with the severity of inflammation and fibrosis on day 92, but not with the number of TGF&beta, 1-expressing cells. Fibrosis correlated significantly with inflammation and fractional dose. In conclusion, the parameter of ear thickness can be used as an objective, numerical and dose-dependent quantification criterion to characterize the severity of acute toxicity and allow for the prediction of late effects.

Supplementation with the antioxidant selenium is frequently performed in breast cancer patients to protect the normal tissue from radiation-induced side effects. However, concerns exist whether selenium also protects tumor cells from radiation-induced cell kill and thereby reduces the efficacy of radiotherapy. In this work, the effect of selenium administration on the radiosensitivity of breast cancer cells was evaluated in vitro. Physiological relevant selenium concentrations (70 and 140 µg/l) did not affect DNA double-strand breaks (γH2AX foci) after 4-Gy X-ray irradiation. Also apoptosis (caspase 3/7) after irradiation with 10 Gy was not influenced by selenium treatment in MDA-MB-231 and MCF7 cells. Most importantly, selenium supplementation did not impair the clonogenic survival of the breast cancer cell lines after irradiation (0, 2, 4, 6, 8 Gy). The data suggest that physiological relevant selenium concentrations administered in combination with radiation therapy do not deteriorate the efficacy of radiotherapy in breast cancer patients. However, randomized clinical trials comparing the effectiveness of radiotherapy and the associated side effects in patients with and without selenium supplementation are recommended.

Microbeam radiation therapy (MRT), a preclinical form of spatially fractionated radiotherapy, uses an array of microbeams of hard synchrotron X-ray radiation. Recently, compact synchrotron X-ray sources got more attention as they provide essential prerequisites for the translation of MRT into clinics while overcoming the limited access to synchrotron facilities. At the Munich compact light source (MuCLS), one of these novel compact X-ray facilities, a proof of principle experiment was conducted applying MRT to a xenograft tumor mouse model. First, subcutaneous tumors derived from the established squamous carcinoma cell line FaDu were irradiated at a conventional X-ray tube using broadbeam geometry to determine a suitable dose range for the tumor growth delay. For irradiations at the MuCLS, FaDu tumors were irradiated with broadbeam and microbeam irradiation at integral doses of either 3Gy or 5Gy and tumor growth delay was measured. Microbeams had a width of 50µm and a center-to-center distance of 350µm with peak doses of either 21Gy or 35Gy. A dose rate of up to 5Gy/min was delivered to the tumor. Both doses and modalities delayed the tumor growth compared to a sham-irradiated tumor. The irradiated area and microbeam pattern were verified by staining of the DNA double-strand break marker γH2AX. This study demonstrates for the first time that MRT can be successfully performed in vivo at compact inverse Compton sources.

A positron timing counter (TC) with 30–40 ps time resolution for 50 MeV/c positrons required by the MEG II experiment has been developed. We employed a highly segmented design with 512 scintillator plates (120 × 40 × 5 mm3 and 120 × 50 × 5 mm3) read out by 6-SiPM-arrays at the both ends. Pile up is reduced by the segmented design and multi-counter measurement improves the overall timing resolution. All the single counters were assembled and their resolutions were measured to be below 100 ps in a pre-test with a 90 Sr source. The construction and installation were completed in 2017. An engineering run was performed at the end of 2017 at the π E5 muon beam line in PSI, which supplies the most intense muon beam (7 × 107 stops/s on a target) in the world. We successfully operated the full system of TC in the MEG II environment and achieved a time resolution below 40 ps with more than 6 counter hits. The overall resolution for the signal positrons is estimated to be 38.5 ps by weighting the obtained resolutions with the number of hits distribution of the signal positrons obtained by a Monte Carlo simulation. The time resolution of the TC is improved by a factor of 2 with respect to the MEG experiment.

International audience; Extraordinary normal tissue response to highly spatially fractionated X-ray beams has been explored for over 25 years. More recently, alternative radiation sources have been developed and utilized with the aim to evoke comparable effects. These include protons, which lend themselves well for this endeavour due to their physical depth dose characteristics as well as corresponding variable biological effectiveness. This paper addresses the motivation for using protons to generate spatially fractionated beams and reviews the technological implementations and experimental results to date. This includes simulation and feasibility studies, collimation and beam characteristics, dosimetry and biological considerations as well as the results of in vivo and in vitro studies. Experimental results are emerging indicating an extraordinary normal tissue sparing effect analogous to what has been observed for synchrotron generated X-ray microbeams. The potential for translational research and feasibility of spatially modulated proton beams in clinical settings is discussed

The achievement and equity gap between majority students and underrepresented minority students, first generation college students, and low socio-economic status undergraduate students is a pervasi...

Aim:Intraoperative allogeneic blood product transfusion (ABPT) in cardiac surgery is associated with worse overall outcome, including mortality. The objective of this study was to evaluate the ABPTs in minimalized extracorporeal cardiopulmonary (MECCTM) compared with standard open system on-pump coronary revascularization.Methods:Data of 156 patients undergoing myocardial revascularization between September 2008 and September 2010 were reviewed. 83 patients were operated by the MECC technique and 73 were treated by standard extracorporeal circulation (sECC). ABPT and overall early postoperative complications were analyzed.Results:Operative mortality and morbidity were similar in both groups. ABPT in the MECC group was significantly lower than in the sECC group both intraoperatively (7.2vs.60.3% of patients pvs.57.5%; pvs.232 ± 45 min; p=0.012), cardiopulmonary bypass (CPB) - (82 ± 25vs.95 ± 26 min; p=0.014), and X-clamp- times (50 ± 16vs.56 ± 17 min; p=0.024) were significantly lower in the MECC group than in the sECC group. Length of ICU (intensive care unit) - and hospital stay were also significantly lower in the MECC groupvs.the sECC group (26.7 ± 20.2vs.54.5 ± 68.9 h; pvs.14.5 ± 4.6 days; pConclusion:Application of MECC as on-pump coronary artery bypass graft (CABG) results in significantly lower ABPT as well as shorter ICU and in-hospital stay. In order to achieve these benefits of MECC autologous retrograde priming, Bispectral index (BIS) monitoring, intraoperative cell salvage, meticulous hemostasis and strict peri- and postoperative volume management are crucial.

Glioblastoma multiforme (GBM) is the most common high-grade intracranial tumor in adults. It is characterized by uncontrolled proliferation, diffuse infiltration due to high invasive and migratory capacities, as well as intense resistance to chemo- and radiotherapy. With a five-year survival of less than 3% and an average survival rate of 12 months after diagnosis, GBM has become a focus of current research to urgently develop new therapeutic approaches in order to prolong survival of GBM patients. The methylation status of the promoter region of the O6-methylguanine–DNA methyltransferase (MGMT) is nowadays routinely analyzed since a methylated promoter region is beneficial for an effective response to temozolomide-based chemotherapy. Furthermore, several miRNAs were identified regulating MGMT expression, apart from promoter methylation, by degrading MGMT mRNA before protein translation. These miRNAs could be a promising innovative treatment approach to enhance Temozolomide (TMZ) sensitivity in MGMT unmethylated patients and to increase progression-free survival as well as long-term survival. In this review, the relevant miRNAs are systematically reviewed.

Cylindrospermopsin (CYN) is a toxin associated with numerous species of freshwater cyanobacteria throughout the world. It is postulated to have caused an episode of serious illnesses in Australia through treated drinking water, as well as lethal effects in livestock exposed to water from farm ponds. Toxicity included effects indicative of both hepatic and renal dysfunction. In humans, symptoms progressed from initial hepatomegaly, vomiting, and malaise to acidosis and hypokalemia, bloody diarrhea, and hyperemia in mucous membranes. Laboratory animal studies predominantly involved the intraperitoneal (i.p.) route of administration and confirmed this pattern of toxicity with changes in liver enzyme activities and histopathology consistent with hepatic injury and adverse renal effects. The aim of this study was designed to assess subchronic oral exposure (90 d) of purified CYN from 75 to 300 µg/kg/d in mouse. At the end of the dosing period, examinations of animals noted (1) elevated organ to body weight ratios of liver and kidney at all dose levels, (2) treatment-related increases in serum alanine aminotransferase (ALT) activity, (3) decreased blood urea nitrogen (BUN) and cholesterol concentrations in males, and (4) elevated monocyte counts in both genders. Histopathological alterations included hepatocellular hypertrophy and cord disruption in the liver, as well as renal cellular hypertrophy, tubule dilation, and cortical tubule lesions that were more prominent in males. A series of genes were differentially expressed including Bax (apoptosis), Rpl6 (tissue regeneration), Fabp4 (fatty acid metabolism), and Proc (blood coagulation). Males were more sensitive to many renal end points suggestive of toxicity. At the end of exposure, toxicity was noted at all dose levels, and the 75 µg/kg group exhibited significant effects in liver and kidney/body weight ratios, reduced BUN, increased serum monocytes, and multiple signs of histopathology indicating that a no-observed-adverse-effect level could not be determined for any dose level.

Background Proton radiotherapy is a form of charged particle therapy that is preferentially applied for the treatment of tumors positioned near to critical structures due to their physical characteristics, showing an inverted depth-dose profile. The sparing of normal tissue has additional advantages in the treatment of pediatric patients, in whom the risk of secondary cancers and late morbidity is significantly higher. Up to date, a fixed relative biological effectiveness (RBE) of 1.1 is commonly implemented in treatment planning systems with protons in order to correct the physical dose. This value of 1.1 comes from averaging the results of numerous in vitro experiments, mostly conducted in the middle of the spread-out Bragg peak, where RBE is relatively constant. However, the use of a constant RBE value disregards the experimental evidence which clearly demonstrates complex RBE dependency on dose, cell- or tissue type, linear energy transfer and biological endpoints. In recent years, several in vitro studies indicate variations in RBE of protons which translate to an uncertainty in the biological effective dose delivery to the patient. Particularly for regions surrounding the Bragg peak, the more localized pattern of energy deposition leads to more complex DNA lesions. These RBE variations of protons bring the validity of using a constant RBE into question. Main body This review analyzes how RBE depends on the dose, different biological endpoints and physical properties. Further, this review gives an overview of the new insights based on findings made during the last years investigating the variation of RBE with depth in the spread out Bragg peak and the underlying differences in radiation response on the molecular and cellular levels between proton and photon irradiation. Research groups such as the Klinische Forschergruppe Schwerionentherapie funded by the German Research Foundation (DFG, KFO 214) have included work on this topic and the present manuscript highlights parts of the preclinical work and summarizes the research activities in this context. Short conclusion In summary, there is an urgent need for more coordinated in vitro and in vivo experiments that concentrate on a realistic dose range of in clinically relevant tissues like lung or spinal cord.

In the framework of the upgrade of the MEG experiment a new trigger system with demanding performances in terms of latency was designed. To achieve the goal of 512 ns latency the serial connections between trigger boards have been optimized so that they only rely on serial to parallel shift registers for the data flow, minimizing the amount of logic to be crossed by data. A dedicated Finite State Machine (FSM) was designed to select the sampling point of the serial stream with respect to an external precision clock used by both transmitter and receiver. As a proof of concept a 16 000 channel weighted waveform sum including pedestal suppression, was computed, resulting in 700 ns of latency.

The WaveDAQ is a full custom, compact and highly integrated trigger and data acquisition system. Despite the decisive urge from the MEG II experiment at PSI aiming at a sensitivity of 6 × 1 0 − 14 on the μ → e γ decay, it is a general purpose device suited for small and medium-sized applications in the range from 16 to about 10 000 channels. It exploits the performance of the DRS4 waveform digitiser with a sampling speed programmable from 1 to 5 GSPS; each input channel can supply HV to arrays of SiPMs and provides a front-end amplification with gains chain in the range from 0.5 up to 100 and GHz bandwidth. Input signals are, in parallel to the DRS4, digitised at 80 MSPS and used in an FPGA-based trigger; fast discriminators associated to each input channel are also used for online reconstruction. This paper presents the WaveDAQ design principles and the results obtained by a demonstrator in the MEG II pre-engineering run in fall 2017 with a homogeneous LXe detector and a plastic scintillation detector both readout by SiPMs and in the tests associated to the Δ E-TOF prototype of the FOOT detector.

Soy biodiesel is the predominant biodiesel fuel used in the USA, but only a few, frequently conflicting studies have examined the potential health effects of its emissions.We combusted petroleum diesel (B0) and fuels with increasing percentages of soy methyl esters (B20, B50 and B100) and determined the mutagenicity-emission factors expressed as revertants/megajoule of thermal energy consumed (rev/MJ(th)).We combusted each fuel in replicate in a small (4.3-kW) diesel engine without emission controls at a constant load, extracted organics from the particles with dichloromethane, determined the percentage of extractable organic material (EOM), and evaluated these extracts for mutagenicity in 16 strains/S9 combinations of Salmonella.Mutagenic potencies of the EOM did not differ significantly between replicate experiments for B0 and B100 but did for B20 and B50. B0 had the highest rev/MJ(th), and those of B20 and B100 were 50% and ∼85% lower, respectively, in strains that detect mutagenicity due to polycyclic aromatic hydrocarbons (PAHs), nitroarenes, aromatic amines or oxidative mutagens. For all strains, the rev/MJ(th) decreased with increasing biodiesel in the fuel. The emission factor for the 16 EPA Priority PAHs correlated strongly (r(2 )= 0.69) with the mutagenicity-emission factor in strain TA100 + S9, which detects PAHs.Under a constant load, soy-biodiesel emissions were 50-85% less mutagenic than those of petroleum diesel. Without additional emission controls, petroleum and biodiesel fuels had mutagenicity-emission factors between those of large utility-scale combustors (e.g. natural gas, coal, or oil) and inefficient open-burning (e.g. residential wood fireplaces).

Der plotzliche Herztod („sudden cardiac death“, SCD) bei jungen Sportlern unter korperlicher Belastung ist mit einer Inzidenz von 1–3 Fallen/100.000 Athleten pro Jahr eine insgesamt seltene Todesursache. Nach der hypertrophen Kardiomyopathie kommt eine Koronaranomalie als zweithaufigste Ursache infrage. Die vorliegende Kasuistik berichtet uber einen 35-jahrigen Mann, der an einem Volkslauf uber die Distanz eines Halbmarathons teilnahm und auf der Zielgeraden kollabierte. Trotz sofortiger Reanimation und initialem „return of spontaneous circulation“ (ROSC) kam es im Verlauf zu einer pulslosen elektrischen Aktivitat (PEA), und die Reanimation wurde 1 h nach Aufnahme in die internistische Schockraumeinheit abgebrochen. Die Autopsie ergab eine Koronaranomalie des interarteriellen Typs „anomalous left coronary artery“ (ALCA). Bei dieser anatomischen Variante kann es unter starker Belastung zu einer Ischamie des jeweiligen Endstromgebiets kommen.

High-precision radiotherapy (RT) requires precise positioning, particularly with high single doses. Fiducial markers in combination with onboard imaging are excellent tools to support this. The purpose of this study is to establish a pancreatic cancer mouse model for high-precision image-guided RT (IGRT) using the liquid fiducial marker BioXmark (Nanovi, Kongens Lyngby, Denmark). In an animal-based cancer model, different volumes of BioXmark (10–50 µl), application forms, and imaging modalities—cone-beam computer tomography (CBCT) incorporated in either the Small Animal Radiation Research Platform (SARRP) or the small-animal micro-CT Scanner (SkyScan; Bruker, Brussels, Belgium)—as well as subsequent RT with the SARRP system were analyzed to derive recommendations for BioXmark. Even small volumes (10 µl) of BioXmark could be detected by CBCT (SARRP and Skyscan). Larger volumes (50 µl) led to hardening artefacts. The position of BioXmark was monitored at least weekly by CBCT and was stable over 4 months. BioXmark was shown to be well tolerated; no changes in physical condition or toxic side effects were observed in comparison to control mice. BioXmark enabled an exact fusion with the original treatment plan with less hardening artefacts, and minimized the application of contrast agent for fractionated RT. An orthotopic pancreatic tumor mouse model was established for high-precision IGRT using a fiducial marker. BioXmark was successfully tested and provides the perfect basis for improved imaging in high-precision RT. BioXmark enables a unique application method and optimal targeted precision in fractionated RT. Therefore, preclinical trials evaluating novel fractionation regimens and/or combination treatment with high-end RT can be performed.

Background and Purpose— In patients who present with acute ischemic stroke while on treatment with non–vitamin K antagonist oral anticoagulants (NOACs), coagulation testing is necessary to confirm the eligibility for thrombolytic therapy. We evaluated the current use of coagulation testing in routine clinical practice in patients who were on NOAC treatment at the time of acute ischemic stroke. Methods— Prospective multicenter observational RASUNOA registry (Registry of Acute Stroke Under New Oral Anticoagulants; February 2012–2015). Results of locally performed nonspecific (international normalized ratio, activated partial thromboplastin time, and thrombin time) and specific (antifactor Xa tests, hemoclot assay) coagulation tests were documented. The implications of test results for thrombolysis decision-making were explored. Results— In the 290 patients enrolled, nonspecific coagulation tests were performed in ≥95% and specific coagulation tests in 26.9% of patients. Normal values of activated partial thromboplastin time and international normalized ratio did not reliably rule out peak drug levels at the time of the diagnostic tests (false-negative rates 11%–44% [95% confidence interval 1%–69%]). Twelve percent of patients apparently failed to take the prescribed NOAC prior to the acute event. Only 5.7% (9/159) of patients in the 4.5-hour time window received thrombolysis, and NOAC treatment was documented as main reason for not administering thrombolysis in 52.7% (79/150) of patients. Conclusions— NOAC treatment currently poses a significant barrier to thrombolysis in ischemic stroke. Because nonspecific coagulation test results within normal range have a high false-negative rate for detection of relevant drug concentrations, rapid drug-specific tests for thrombolysis decision-making should be established. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01850797.

Purpose Tumor cells, in contrast to normal cells, frequently overexpress heat shock protein 70 (Hsp70) in the cytosol, present it on their cell surface, and actively release it. Therefore, soluble Hsp70 (sHsp70) was investigated as a potential tumor biomarker for monitoring the outcome of radiation therapy. Methods and Materials Plasma from mice bearing membrane Hsp70 (mHsp70)-positive FaDu human squamous cell carcinoma of the head and neck and spontaneous pancreatic ductal adenocarcinoma (PDAC) was investigated. A cohort of mice with FaDu tumors (0.32 cm 3 ) was irradiated with 30 Gy, and plasma was collected 24 hours after irradiation, after the tumors had shrunk to 50% of their starting volume and after complete remission. sHsp70 levels in the plasma were quantified by enzyme-linked immunosorbent assay. Results sHsp70 levels were significantly higher in the blood of tumor-bearing mice than that of control animals. A correlation between increasing sHsp70 plasma levels and tumor volume in the range of 0.01 cm 3 to 0.66 cm 3 was observed. Radiation-induced regression of the tumors was associated with significantly decreased sHsp70 levels, which returned to the level of control animals after complete remission. Conclusion We propose sHsp70 as an innovative biomarker for detecting tumors and for monitoring the clinical outcome of radiation therapy in cancer patients.

We present the new TDAQ system designed for the upgraded MEG experiment, MEG II. It is an assembly of three new boards in a dedicated crate. The system foundation is on the so called WaveDREAM board with DAQ and trigger capabilities accompanied by trigger concentrator boards, to collect information from the detectors and perform real time event reconstruction, and data concentrator boards for DAQ purposes. The designed system, despite having been conceived for the MEG II experiment, is particularly flexible and can be utilised in many small and medium size applications, from a few up to many thousands of channels. We present the development status and the results from the first data acquisition beam test of a full crate with one of the MEG II detectors.

PURPOSE: Proton minibeam radiation therapy is a novel approach to minimize normal tissue damage in the entrance channel by spatial fractionation while keeping tumor control through a homogeneous tumor dose using beam widening with an increasing track length. In the present study, the dose distributions for homogeneous broad beam and minibeam irradiation sessions were simulated. Also, in an animal study, acute normal tissue side effects of proton minibeam irradiation were compared with homogeneous irradiation in a tumor-free mouse ear model to account for the complex effects on the immune system and vasculature in an invivo normal tissue model. METHODS AND MATERIALS: At the ion microprobe SNAKE, 20-MeV protons were administered to the central part (7.2×7.2mm(2)) of the ear of BALB/c mice, using either a homogeneous field with a dose of 60Gy or 16 minibeams with a nominal 6000Gy (4×4 minibeams, size 0.18×0.18mm(2), with a distance of 1.8mm). The same average dose was used over the irradiated area. RESULTS: No ear swelling or other skin reactions were observed at any point after minibeam irradiation. In contrast, significant ear swelling (up to fourfold), erythema, and desquamation developed in homogeneously irradiated ears 3 to 4weeks after irradiation. Hair loss and the disappearance of sebaceous glands were only detected in the homogeneously irradiated fields. CONCLUSIONS: These results show that proton minibeam radiation therapy results in reduced adverse effects compared with conventional homogeneous broad-beam irradiation and, therefore, might have the potential to decrease the incidence of side effects resulting from clinical proton and/or heavy ion therapy.

Summary The determination of grain boundary planes in multicrystalline material has only been restricted to transmission electron microscope investigations (Jang et al., 1992; Elgat et al., 1985) or to metallograpical investigations of the grain boundary (Randle et al., 1993). The first method is expensive, and both are complex and time consuming in grain boundary preparation. This paper proposes the determination of grain boundary planes in semiconductor wafer by a combined application of Electron Back Scatter Diffraction and Infrared Transmission Microscopy. In particular, the new method is demonstrated with directional solidificated multicrystalline silicon.

To examine if the sequential treatment of Avastin and Macugen is safe and more efficient than the mono-therapies in a prospective randomized masked pilot study.Subjects with exudative age-related macular degeneration were randomized to receive three intravitreal injections of either 1 mg of Avastin, 0.3 mg Macugen, or first 1 mg Avastin followed by retreatment of 0.3 mg Macugen. Follow-up examinations were performed after 1, 6, 12 weeks, and 6 months.Forty-eight subjects were included (13:18:17). Avastin resulted in lasting significant changes in visual acuity at 6 weeks, increase in contrast sensitivity at 6 weeks, and a significant decrease in macular thickness after 6 and 12 weeks. Macugen showed a significant decrease in retinal thickness after 6 weeks, but a significant decrease in visual acuity after 6 months, and a significant decrease in contrast sensitivity after 12 weeks and 6 months. The sequential treatment showed a decrease in retinal thickness after 1 and 12 weeks.Avastin alone is more effective in increasing visual acuity and contrast sensitivity and decreasing retinal thickness, than Macugen or the sequential treatment. We conclude that the sequential treatment of Avastin with Macugen is safe, but the single treatment of Avastin is more efficient.

EIGER is an advanced family of single photon counting hybrid pixel detectors, primarily aimed at diffraction experiments at synchrotrons. Optimization of maximal functionality and minimal pixel size (using a 0.25 μ m process and conserving the radiation tolerant design) has resulted in 75 × 75 μ m 2 pixels. Every pixel comprises a preamplifier, shaper, discriminator (with a 6 bit DAC for threshold trimming), a configurable 4/8/12 bit counter with double buffering, as well as readout, control and test circuitry. A novel feature of this chip is its double buffered counter, meaning a next frame can be acquired while the previous one is being readout. An array of 256×256 pixels fits on a ∼ 2 × 2 cm 2 chip and a sensor of ∼ 8 × 4 cm 2 will be equipped with eight readout chips to form a module containing 0.5 Mpixel. Several modules can then be tiled to form larger area detectors. Detectors up to 4×8 modules (16 Mpixel) are planned. To achieve frame rates of up to 24 kHz the readout architecture is highly parallel, and the chip readout happens in parallel on 32 readout lines with a 100 MHz Double Data Rate clock. Several chips and singles (i.e. a single chip bump-bonded to a single chip silicon sensor) were tested both with a lab X-ray source and at Swiss Light Source (SLS) beamlines. These tests demonstrate the full functionality of the chip and provide a first assessment of its performance. High resolution X-ray images and “high speed movies” were produced, even without threshold trimming, at the target system frame rates (up to ∼ 24 kHz in 4 bit mode). In parallel, dedicated hardware, firmware and software had to be developed to comply with the enormous data rate the chip is capable of delivering. Details of the chip design and tests will be given, as well as highlights of both test and final readout systems.

Background Fuchs’s corneal dystrophy (FCD) is a leading cause of corneal transplantation and affects 5% of persons in the United States who are over the age of 40 years. Clinically visible deposits called guttae develop under the corneal endothelium in patients with FCD. A loss of endothelial cells and deposition of an abnormal extracellular matrix are observed microscopically. In advanced disease, the cornea swells and becomes cloudy because the remaining endothelial cells are not sufficient to keep the cornea dehydrated and clear. Although rare genetic variation that contributes to both early-onset and typical late-onset forms of FCD has been identified, to our knowledge, no common variants have been reported. Methods We performed a genomewide association study and replicated the most significant observations in a second, independent group of subjects. Results Alleles in the transcription factor 4 gene (TCF4), encoding a member of the E-protein family (E2-2), were associated with typical FCD (P = 2.3×10 −26 ). The association increased the odds of having FCD by a factor of 30 for persons with two copies of the disease variants (homozygotes) and discriminated between case subjects and control subjects with about 76% accuracy. At least two regions of the TCF4 locus were associated independently with FCD. Alleles in the gene encoding protein tyrosine phosphatase receptor type G (PTPRG) were associated with FCD (P = 4.0×10 −7 ), but the association did not reach genomewide significance. Conclusions Genetic variation in TCF4 contributes to the development of FCD. (Funded by the National Eye Institute and others.)

Background: Epidemiological screening to examine possible ultraviolet-induced ocular changes and pathologies in Austrian farmers. Methods: The study was performed on behalf of the Austrian farmer insurance (Sozialversicherungsanstalt der Bauern). Randomly selected farmers and office workers as controls, both at the age of 35–55 years, underwent ophthalmic screening examinations. All subjects underwent complete ophthalmic examinations by slit lamp examination and Schirmer’s test 1. A survey, regarding per- sonal habits in the sun, was also conducted. Results: Three hundred and ninety-two subjects underwent ophthalmic examinations of whom 297 were farmers and 95 were controls. Due to the survey, 89.7% of the farmers claimed to protect themselves from the sun during work. From these subjects, 83.7% wear a head protection, 71.0% wear sunglasses, and 54.4% usually work in the shade. There were significant differences in lid (p = 0.021) and conjunctival pathologies (p < 0.0001) between farmers and controls. Conclusion: Austrian farmers are at a higher risk for developing lid and conjunctival tumours which require treatment at some point. We believe that the study group was too young to show significant differences within the lens and the posterior pole. A 5-year follow-up is planned.

To compare possible toxic effects of membrane blue and infracyanine green used as vital stains in macular surgery. Vital stains are used in vitreoretinal surgery to perform peeling of the internal limiting membrane and idiopathic epiretinal membrane. There are many controversial studies about their toxicity, safety, and their effects on the retinal pigment epithelium and the neuroretinal elements. To compare possible toxicities of the two vital stains membrane blue and infracyanine green in vivo, we conducted a prospective, randomized, clinical trial.A prospective, randomized clinical trial including 30 eyes of 30 patients with either full-thickness macular hole or idiopathic epiretinal membrane were included and randomized 1:1 to receive either membrane blue or infracyanine green during vitreoretinal surgery. Complete ophthalmic examinations, including optical coherence tomography and peripheral visual field were performed preoperatively, and 1, 3, and 6 months postoperatively in our clinic. The main outcome measure was the peripheral visual field. Data was analysed with Student's t-test and Pearson's correlation coefficient.Three months after surgery there was a significant difference in increase in visual field in the superior region in favor of the membrane blue group (p = 0.021). Eight eyes (53%) of the infracyanine group had a decrease in temporal visual fields of at least 5 degrees .Although there was a significant difference in visual fields between the groups after 3 months in the superior region, there were no more significant differences between the two groups after 6 months. However, due to the decrease in the temporal visual field in some eyes, we conclude that membrane blue is less toxic.

The aim of this study was to investigate and quantify two biomarkers for radiation exposure (dicentrics and gamma-H2AX foci) in human lymphocytes after CT scans in the presence of an iodinated contrast agent. Blood samples from a healthy donor were exposed to CT scans in the absence or presence of iotrolan 300 at iodine concentrations of 5 or 50 mg ml(-1) blood. The samples were exposed to 0.025, 0.05, 0.1 and 1 Gy in a tissue equivalent body phantom. Chromosome aberration scoring and automated microscopic analysis of gamma-H2AX foci were performed in parts of the same samples. The theoretical physical dose enhancement factor (DEF) was calculated on the basis of the mass energy-absorption coefficients of iodine and blood and the photon energy spectrum of the CT tube. No significant differences in the yields of dicentrics and gamma-H2AX foci were observed in the absence or presence of 5 mg iodine ml(-1) blood up to 0.1 Gy, whereas at 1 Gy the yields were elevated for both biomarkers. At an iodine concentration of 50 mg ml(-1) serving as a positive control, a biological DEF of 9.5 +/- 1.4 and 2.3 +/- 0.5 was determined for dicentrics and gamma-H2AX foci, respectively. A physical DEF of 1.56 and 6.30 was calculated for 5 and 50 mg iodine ml(-1), respectively. Thus, it can be concluded that in the diagnostic dose range (radiation and contrast dose), no relevant biological dose-enhancing effect could be detected, whereas a clear biological dose-enhancing effect could be found for a contrast dose well outside the diagnostic CT range for the complete radiation dose range with both methods.

This study investigates the effects of workers' perceived participation in democratic decision-making on their prosocial behavioral orientations, democratic values, commitment to the firm, and perceptions of socio-moral climate. The sample consists of 325 German-speaking employees from 22 companies in Austria, North Italy, and Southern Germany that vary in their level of organizational democracy (social partnership enterprises, workers' co-operatives, democratic reform enterprises, and employee-owned self-governed firms). The findings suggest that the extent employees participate in democratic forms of organizational decision-making is positively related to the firm's socio-moral climate as well as to their own organizational commitment and prosocial and community-related behavioral orientations. The results also indicate that socio-moral climate is positively related to employees' organizational commitment. The effect of participation in decision-making on organizational commitment is partially mediated by socio-moral climate. Implications for promoting societal and organizational civic virtues among individuals are described. Copyright © 2009 John Wiley & Sons, Ltd.

Advances in threats, geopolitical developments, and commercial technologies continually challenge combat system stability because they constantly create new demands and therefore requirements for the system. Because the life cycle of major Department of Defense (DoD) systems can last decades, long-fielded systems in particular are vulnerable to requirements creep. One technique to mitigate the impact requirements volatility can have on a system is through the implementation of technologies that have been developed to allow the system to adapt while minimizing the effect of change on the system as a whole. This paper investigates the application of one such technology-Rules Engine-to the Decision Automation domain of two Navy combat systems. This paper also proposes modifications to the systems engineering process given that using change-tolerant technologies affects the way a system can be developed and maintained.

Purpose: Melatonin (N-acetyl-5-methoxytryptamine) (MT) is a hormone that acts as an antioxidant. It is produced by the pineal gland and within the retina; its release is blocked by light entering the eye. We examined whether MT daytime levels differ between pseudophakic patients with age-related macular degeneration (ARMD) and pseudophakic subjects without any ocular pathology of the same age. Methods: A prospective, cross-sectional, observational study was performed. Pseudophakic patients of the same age group were included. Patients underwent complete ophthalmic examinations and blood sampling between 08:00 and 10:00 hr. MT daytime value in the serum was the main outcome measure. Results: Sixty-nine pseudophakic patients were included. Fifty patients with exudative and non-exudative ARMD were in the study group while 19 patients were controls. Patients with ARMD had significantly higher daytime levels of MT (P = 0.003). There were significant differences in MT daytime levels between the exudative and non-exudative forms (P = 0.009). MT values also correlated with the best-corrected visual acuity (r = )0.285, P = 0.019). Conclusion: These data indicate that pseudophakic patients with ARMD produce more MT during the day compared to pseudophakic subjects without ARMD. This may be caused by the reduced visual acuity in patients with ARMD, whereby less light reaches the photoreceptors, allowing MT secretion to continue during the day. Because MT also acts as an antioxidant and daytime levels are higher in patients with ARMD, these results might be interpreted as a rescue factor.

To investigate the association of the complement factor H gene (CFH)Y402H polymorphism and age-related macular degeneration (AMD) in the Austrian population (Caucasoid descent), and to determine whether there is an association between exposure to Chlamydia pneumoniae-responsible for up to 20% of community-acquired pneumoniae-and the AMD-associated CFHrisk polymorphism.Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis in 75 unrelated AMD patients and compared with 75 healthy, age-matched control subjects. C. pneumoniaeserum IgG was tested by ELISA (RD) in both groups. The association between the CFHY402H genetic polymorphism and the disease was examined by chi (2)-test and logistic regression.CFH Y402H genotypefrequencies differed significantly between AMD patients and healthy controls (1277 TT, 22.7%; 1277 TC, 53.3%; and 1277 CC, 22.7% in the AMD group; 1277 TT, 48.0%; 1277 TC, 38.7%; and 1277 CC, 13.3% in the control group) showing a P-value0.005 (OR:2.920/3.811).No association was found between a positive C. pneumoniae titre and AMD (P=0.192), nor was any association found between C. pneumoniae and the CFH Y402H polymorphism.Our data confirm that the CFHY402H polymorphism is a risk factor for AMD in the Austrian population with a higher frequency of the Y402 polymorphism in AMD patients. No association between preceding C. pneumoniaeinfection and diagnosed AMD was found.

BACKGROUND: To examine macular thickness changes after uncomplicated cataract surgery in healthy patients and patients with diabetes mellitus and/or arterial hypertension without ocular manifestation. SETTING: Department of Ophthalmology, Rudolf Foundation Clinic, Ludwig Boltzmann Institute of Retinology and Biomicroscopic Lasersurgery, Vienna, Austria. METHODS: Prospective study with uneventful cataract surgery. Patients were subdevided into two groups. In group one, we included 10 patients without any general internal disease, in group two 15 patients with diabetes and/or arterial hypertension without ocular pathologies. Patients were examined preoperatively, one day, 1, 4 and 12 weeks postoperatively. At each visit a complete ophthalmic evaluation, best corrected Snellen visual acuity and optical coherence tomography of the macula were performed. RESULTS: Twenty-five eyes of 25 patients were recruited. The mean age was 70 ± 10 years. The average preoperative foveal thickness in both groups was 164 µm ± 12. The foveal thickness four weeks after surgery was 167 ± 14 (p = 0.64) in group 1 and 173 µm ± 14 (p = 0.08) in group 2. One eye in each group had decreased visual results 1 week postoperatively with subclinical thickening of the central macula in OCT measurement. CONCLUSION: We found no significant increase of foveal thickness after uneventful cataract surgery in both groups and there was no significant difference between these groups. However the percentage of eyes with foveal thickening was higher in group 2 than in group 1 (60% to 20% after 4 weeks and 47% to 30% 12 weeks after surgery).

Self-focusing of few-cycle pulses in atmospheric-pressure argon results in a supercontinuum which differs remarkably from the case of longer pulses: under single-filament conditions it extends to 200 nm and 250 nm with 6 fs and 10 fs pulses, respectively; the radiation, including the shortest wavelengths, is collimated and shows no conical emission. The short-wavelength part is intrinsically at least as short as the incoming fundamental pulse. These features make the few-cycle supercontinuum attractive as a source of widely tunable 10 fs pump pulses for spectroscopic applications. We present extensive experimental results including the dependence of the spectrum on pulse energy, duration and chirp, filament length, gas pressure and a comparison with nitrogen and air. We discuss them and other features including the role of the third harmonic and identify the conditions required to get a single highly stable filament. We also present a model, based on self-guiding, which predicts useful scaling rules.

Die Entstehung hormonrefraktarer Prostatakarzinomzellen wahrend einer Hormonablationstherapie stellt die Hauptursache fur den Tumorprogress und die hohe Mortalitatsrate des fortgeschrittenen Prostatakarzinoms (PCA) dar. Wahrend in vitro der Verlust des Androgenrezeptors (AR) der vorherrschende Mechanismus fur die Entwicklung einer Hormoninsensitivitat ist, zeigen In-vivo-Untersuchungen, dass die Expression des AR in Zellen hormonrefraktarer PCA weitgehend erhalten bleibt oder sogar gesteigert ist. Die im Hinblick auf die in westlichen Industrienationen kontinuierlich steigende Anzahl an PCA durchgefuhrten molekularbiologischen bzw. zellbiologischen Untersuchungen fuhrten zur Entdeckung einer Vielzahl neuer Faktoren/Mechanismen, die bei der Entstehung hormonrefraktarer PCA eine Rolle spielen. Diese Erkenntnisse sollten in weiterer Folge zu neuen Therapiekonzepten fuhren bzw. solche unterstutzen.

BACKGROUND: The major stress-inducible heat shock protein 70 (Hsp70) is frequently overexpressed in the cytosol and integrated in the plasma membrane of tumor cells via lipid anchorage. Following stress such as non-lethal irradiation Hsp70 synthesis is up-regulated. Intracellular located Hsp70 is known to exert cytoprotective properties, however, less is known about membrane (m)Hsp70. Herein, we investigate the role of mHsp70 in the sensitivity towards irradiation in tumor sublines that differ in their cytosolic and/or mHsp70 levels. METHODS: The isogenic human colon carcinoma sublines CX(+) with stable high and CX(-) with stable low expression of mHsp70 were generated by fluorescence activated cell sorting, the mouse mammary carcinoma sublines 4T1 (4T1 ctrl) and Hsp70 knock-down (4T1 Hsp70 KD) were produced using the CRISPR/Cas9 system, and the Hsp70 down-regulation in human lung carcinoma sublines H1339 ctrl/H1339 HSF-1 KD and EPLC-272H ctrl/EPLC-272H HSF-1 KD was achieved by small interfering (si)RNA against Heat shock factor 1 (HSF-1). Cytosolic and mHsp70 was quantified by Western blot analysis/ELISA and flow cytometry; double strand breaks (DSBs) and apoptosis were measured by flow cytometry using antibodies against γH2AX and real-time PCR (RT-PCR) using primers and antibodies directed against apoptosis related genes; and radiation sensitivity was determined using clonogenic cell surviving assays. RESULTS: CX(+)/CX(-) tumor cells exhibited similar cytosolic but differed significantly in their mHsp70 levels, 4T1 ctrl/4T1 Hsp70 KD cells showed significant differences in their cytosolic and mHsp70 levels and H1339 ctrl/H1339 HSF-1 KD and EPLC-272H ctrl/EPLC-272H HSF-1 KD lung carcinoma cell sublines had similar mHsp70 but significantly different cytosolic Hsp70 levels. γH2AX was significantly up-regulated in irradiated CX(-) and 4T1 Hsp70 KD with low basal mHsp70 levels, but not in their mHsp70 high expressing counterparts, irrespectively of their cytosolic Hsp70 content. After irradiation γH2AX, Caspase 3/7 and Annexin V were up-regulated in the lung carcinoma sublines, but no significant differences were observed in H1339 ctrl/H1339 HSF-1 KD, and EPLC-272H ctrl/EPLC-272H HSF-1 KD that exhibit identical mHsp70 but different cytosolic Hsp70 levels. Clonogenic cell survival was significantly lower in CX(-) and 4T1 Hsp70 KD cells with low mHsp70 expression, than in CX+ and 4T1 ctrl cells, whereas no difference in clonogenic cell survival was observed in H1339 ctrl/H1339 HSF-1 KD and EPLC-272H ctrl/ EPLC-272H HSF-1 KD sublines with identical mHsp70 but different cytosolic Hsp70 levels. CONCLUSION: In summary, our results indicate that mHsp70 has an impact on radiation resistance.

Focusing 800-nm pulses of 10–20 fs and ≤0.4 mJ into atmospheric-pressure argon gives rise to a supercontinuum extending down to 250 nm. We show that spectral cuts from this radiation can be shortened by a simple prism compressor down to 30 fs even near the UV cut-off. The resulting pulses have enough energy (several hundred nanojoules) to serve as a simple and rugged broadly tunable pump source in ultra-fast transient spectroscopy. Such an application is demonstrated for the first time, using pulses tuned over 280–320 nm to excite Cr(CO)6; probing it by intense-field ionization at 800 nm, we determine the lifetime of initially populated states to be as short as 14 fs.

Die standig wachsende Liste an Chemotherapeutika veranlasste uns eine aktuelle Ubersichtsarbeit, welche die Nebenwirkungen im Augenbereich darstellt, zu verfassen. Da das Sehvermogen eine Lebensqualitat ist, die im Rahmen von Voruntersuchungen und eventuellen regelmasigen Kontrollen erhalten werden kann, ist es fur den Onkologen als auch fur den Ophthalmologen wichtig, dass beide uber die Augennebenwirkungen der gelaufigen Chemotherapeutika Bescheid wissen. Eine Fruherkennung und rechtzeitige Behandlung der Nebenwirkungen im Augenbereich kann oftmals den Sehverlust oder bleibende Folgeschaden verhindern. Es wurde eine Ubersichtsarbeit verfasst, die alle Augennebenwirkungen der heute verwendeten Chemotherapeutika zusammenfasst. Die Literatursuche wurde im MEDLINE durchgefuhrt und die Ubersichtsarbeit beinhaltet alle beschriebenen Augennebenwirkungen von 1966 bis August 2003. Die Chemotherapeutika wurden nach ihren verschiedenen Wirkungsmechanismen in folgende Gruppen eingeteilt: Alkylantien, Antimetabolite, Mitose Inhibitoren, Antibiotika und hormonelle Antagonisten. Bei jeder Substanz wird kurz die Verwendung und der Wirkmechanismus beschrieben, bevor auf die Augennebenwirkungen eingegangen wird. Geringgradige Nebenwirkungen im Augenbereich kommen haufig bei niedrig dosierten Chemotherapien vor. Diese sind aber meist reversibel und verschwinden auch schnell wieder nach Beendigung der Therapie. Hochdosierte Chemotherapien, starke Kombinationstherapien und intraarterielle Verabreichung mancher Substanzen kann hingegen irreversible Schaden zur Folge haben. Bei der rechtzeitigen Erkennung solcher Nebenwirkungen muss eine Dosisreduzierung oder sogar Therapieunterbrechung in Betracht gezogen werden, um den Sehverlust zu verhindern. Onkologen und Ophthalmologen sollten sich uber die Augennebenwirkungen von Chemotherapien bewusst sein. Durch eine ophthalmologische Voruntersuchung, vor Beginn der Chemotherapie, konnen gefahrdete Patienten ermittelt und zu Kontrolluntersuchungen wiederbestellt werden. Bei manchen Chemotherapieschemen sind laufende Kontrolluntersuchungen ohnehin zu empfehlen. Bei Auftreten von gravierenden Augennebenwirkungen soll auf jeden Fall an eine Dosisreduzierung, oder sogar an eine Therapieunterbrechung gedacht werden, da es bei der Tumorbekampfung auch zum Sehverlust kommen kann. The constantly growing list of cytotoxic chemotherapeutics affords a new survey of ophthalmic complications, which are often underestimated. Vision is a quality of life, which needs to be taken care of, especially if loss of vision can be prevented. The broad spectrum of ophthalmic complications, induced by cytotoxic chemotherapy, includes reversible and irreversible, acute and chronic disorders. A review of the literature reporting ophthalmic complications of currently used cytotoxic chemotherapeutics in oncology was conducted. Literature was searched in Medline from 1995 until August 2003. Further literature was then found in the references of the pre-selected literature. Ophthalmic complications of low-grade, induced by cytotoxic chemotherapy, are very common and reversible after cessation of anticancer therapy. Some major ocular toxicities may even afford a dose reduction or discontinuation of cytotoxic chemotherapy, in order to impede loss of vision. Oncologists and ophthalmologists must be aware of potential ophthalmic complications during cytotoxic chemotherapy. Ocular toxicities can be treated or even prevented, if detected on time, which is why immediate consultation of an ophthalmologist seems to be necessary, as soon as symptoms are recognized. An ophthalmic baseline examination, prior to anticancer treatment, may also lead to a reduction of ocular side effects.