Proton beam quality enhancement by spectral phase control of a PW-class laser system.

We report on experimental investigations of proton acceleration from solid foils irradiated with PW-class laser-pulses, where highest proton cut-off energies were achieved for temporal pulse parameters that varied significantly from those of an ideally Fourier transform limited (FTL) pulse. Controlled spectral phase modulation of the driver laser by means of an acousto-optic programmable dispersive filter enabled us to manipulate the temporal shape of the last picoseconds around the main pulse and to study the effect on proton acceleration from thin foil targets. The results show that applying positive third order dispersion values to short pulses is favourable for proton acceleration and can lead to maximum energies of 70 MeV in target normal direction at 18 J laser energy for thin plastic foils, significantly enhancing the maximum energy compared to ideally compressed FTL pulses. The paper further proves the robustness and applicability of this enhancement effect for the use of different target materials and thicknesses as well as laser energy and temporal intensity contrast settings. We demonstrate that application relevant proton beam quality was reliably achieved over many months of operation with appropriate control of spectral phase and temporal contrast conditions using a state-of-the-art high-repetition rate PW laser system.

Knowledge transfer as a tool towards improvement of cancer care in low- and middle-income countries. 6th European Roundtable Meeting (ERTM), June 14th, 2019, Berlin, Germany.

PURPOSE: To identify key factors for the best practice of knowledge transfer from high-income settings to low- and middle-income settings. RESULTS: Interactive sessions led to the identification of European learnings that can and should be shared beyond Europe. Furthermore, methods were characterised which may lead to successful knowledge transfer with subsequent quality improvement. CONCLUSION: To ensure successful implementation of knowledge and new methods, political support is extremely important. A strong focus should be an improvement of collaboration and network development. Rehabilitation, early and late pallative care, cost effectiveness and long-term follow-up are priorities. Limitations are budget constraints which limit the execution of NCCPs.

Demonstration of a beam loaded nanocoulomb-class laser wakefield accelerator.

Laser-plasma wakefield accelerators have seen tremendous progress, now capable of producing quasi-monoenergetic electron beams in the GeV energy range with few-femtoseconds bunch duration. Scaling these accelerators to the nanocoulomb range would yield hundreds of kiloamperes peak current and stimulate the next generation of radiation sources covering high-field THz, high-brightness X-ray and γ-ray sources, compact free-electron lasers and laboratory-size beam-driven plasma accelerators. However, accelerators generating such currents operate in the beam loading regime where the accelerating field is strongly modified by the self-fields of the injected bunch, potentially deteriorating key beam parameters. Here we demonstrate that, if appropriately controlled, the beam loading effect can be employed to improve the accelerator's performance. Self-truncated ionization injection enables loading of unprecedented charges of ∼0.5 nC within a mono-energetic peak. As the energy balance is reached, we show that the accelerator operates at the theoretically predicted optimal loading condition and the final energy spread is minimized.Higher beam quality and stability are desired in laser-plasma accelerators for their applications in compact light sources. Here the authors demonstrate in laser plasma wakefield electron acceleration that the beam loading effect can be employed to improve beam quality by controlling the beam charge.

Current developments in cancer care: including the patients' perspective-3rd European Roundtable Meeting (ERTM) June 17, 2016, Berlin, Germany.

PURPOSE: National Cancer Control Plans (NCCP) are necessary to improve cancer care and reduce mortality. We have reported previously on European institutional health structures and transformation of theoretical health care standards into a practical approach. For the latter consideration of the patients' perspective was considered as highly important and chosen as subject for this meeting. RESULTS: Several European organizations have realized deficits in this area. They promote equal and timely access to cancer care since current inequities lead to disparities in cancer survival across Europe. Patients' support working groups are focussing on employment issues, financial services, psychosocial screening and support, palliative care and rehabilitation. They also identified cancer research including patients' views as highly important. Workshops during the 3rd European Roundtable Meeting (ERTM) covered the issues transparency in patient care, implementation of new knowledge and decision making in partnership with the patient. CONCLUSIONS: It was concluded that patient views and perspectives have to be considered during the whole continuum of cancer care. Access to treatment, transparency and including patients into the development process are relevant aspects.

[Organized Post-Stroke Care through Case Management on the Basis of a Standardized Treatment Pathway : Results of a Single-Centre Pilot Study]. / Koordinierte Schlaganfallnachsorge durch Case Management auf der Basis eines standardisierten Behandlungspfades : Ergebnisse einer monozentrischen Pilotstudie.

BACKGROUND: Post-stroke care programs based on a standardized treatment pathway supported by case management may prevent secondary stroke and minimize risk factors. OBJECTIVES: We aimed to determine the feasibility of a standardized treatment pathway and its impact on risk factor control, life-style changes and adherence to secondary prevention medication. METHODS: We conducted a prospective pilot study in consecutive stroke patients. The 12-month post-stroke care program included regular perosnal and phone contact with a certified case manager. Target values for vascular risk factors following current recommendations of stroke guidelines were monitored and treated if necessary. In the case of deviations from the treatment pathway the case manager intervened. Patients were screened for recurrent stroke at the end of the program after 12 months. RESULTS: We enrolled 101 patients: 57.4 % were male, the median age was 72 (IQR, 62-80) years, median baseline NIHSS score was 2(IQR, 1-5), 79.2 % had an ischemic stroke, 3 % a hemorrhagic stroke, and 17.8 % a transient ischemic attack (TIA). Eighty-six (85.1 %) patients completed the program, 12 (11.9 %) withdrew from the program and 3 died of malignant diseases. In total, 628 personal (6.2/patient) and 2,683 phone contacts (26.6/patient) were conducted by the case manager. Three hundred-seventy-nine specific interventions were necessary mostly because of missing medication, non-compliance, and social needs. After 12 months, target goals for blood pressure, body mass index, nicotine use, and cholesterol were more frequently (p < 0.05) achieved than at baseline. No recurrent stroke occurred during the program. CONCLUSIONS: Our pilot data demonstrate that case management-based post-stroke care is feasible and may contribute to effective secondary prevention of stroke.

Improving structural development in oncology: transformation of theoretical health care standards and knowledge into a practical approach -- 2nd European Roundtable Meeting (ERTM), May 8, 2015, Berlin, Germany.

PURPOSE: It is widely accepted that National Cancer Control Plans (NCCPs) are essential to improve cancer care. They often describe the structural requirements such as cancer centers, clinical cancer registries and quality control. During the 2nd European roundtable meeting, the implementation processes were analyzed and discussed. RESULTS: Communication strategies between cancer registries and cancer centers need to be developed. Analyses and discussion of collected data have to be performed by multidisciplinary teams. This has to be followed by appropriate actions to improve quality of care. It is essential to describe the clinical procedures, organizational processes and communication between individuals and professional teams. The patients' perspectives have to be included in the development of cancer care networks. The patients' feedback on cancer care is a routine quality indicator. CONCLUSION: NCCPs that include the description of structural requirements are important. In addition, it is essential to develop cancer care networks including multidisciplinary organizational processes to guarantee high quality. These have to consider patients preferences.

Improving cancer care in Europe: Which institutional health structures might be beneficial and why? 1. European Roundtable Meeting (ERTM), 16th May 2014, Berlin, Germany.

PURPOSE: Bringing the knowledge and expertise of different European countries and the European Commission together for an analysis of the different factors being beneficent or rather opposing for high quality in cancer care. A specific focus is set on the structures and views in European nations on implementation processes. RESULTS: Due to the variation of National Cancer Control Plans (NCCPs) the preferences for implementation strategies differ. For quality achievement the involvement of the different stakeholders is beneficial. Common sense was the importance of NCCPs. However, it was consensus between participants that a bottom-up approach that considers the needs of different professional groups involved in cancer care and also the views of patients is of critical importance for successful implementation. Functioning cancer registries and evidence-based guidelines with standard of care are fundamental for quality measurement. CONCLUSIONS: There is consensus between participants of the meeting that NCCPs are essential for improvement of cancer care. However, national preferences and the views of patients and caregivers have to be included to guarantee successful implementation.

Large hospital outbreak of KPC-2-producing Klebsiella pneumoniae: investigating mortality and the impact of screening for KPC-2 with polymerase chain reaction.

BACKGROUND: Multi-drug-resistant Klebsiella pneumoniae carbapenemase (KPC)-2-producing K. pneumoniae are an increasing cause of healthcare-associated infections worldwide. AIMS: To investigate the impact of clinical infection on mortality, and examine the effect of use of KPC-2-specific polymerase chain reaction (PCR) on the time to contact isolation during an outbreak. METHODS: Cases were defined as patients clinically infected or colonized with KPC-2-producing K. pneumoniae between June 2010 and July 2012. Cases were described by demographic and health characteristics, and the association between infection and mortality, adjusted for comorbidities and demographic characteristics, was determined using Poisson regression with robust standard errors. A comparison was made between the time to contact isolation with a culture-based method and PCR using Wilcoxon's rank sum test. FINDINGS: Of 72 cases detected, 17 (24%) had undergone transplantation and 21 (29%) had a malignancy. Overall, 35 (49%) cases were clinically infected, with pneumonia and sepsis being the most common infections. Infection was an independent risk factor for mortality (risk ratio 1.67, 95% confidence interval 0.99-2.82). The median time to contact isolation was 1.5 days (range 0-21 days) using PCR and 5.0 days (range 0-39 days) using culture-based methods (P = 0.003). Intermittent negative tests were observed in 48% (14/29) of cases tested using culture-based methods. CONCLUSION: KPC-2-producing K. pneumoniae mainly affect severely ill patients. Half of the cases developed clinical infection, associated with increased risk of death. As PCR accelerates isolation and provides the opportunity for preventive measures in colonized cases, its use should be implemented promptly during outbreaks. Further studies are needed to enhance knowledge about KPC detection patterns and to adjust screening guidelines.

Influence of experimental conditions on data variability in the liver comet assay.

The in vivo comet assay has increasingly been used for regulatory genotoxicity testing in recent years. While it has been demonstrated that the experimental execution of the assay, for example, electrophoresis or scoring, can have a strong impact on the results; little is known on how initial steps, that is, from tissue sampling during necropsy up to slide preparation, can influence the comet assay results. Therefore, we investigated which of the multitude of steps in processing the liver for the comet assay are most critical. All together eight parameters were assessed by using liver samples of untreated animals. In addition, two of those parameters (temperature and storage time of liver before embedding into agarose) were further investigated in animals given a single oral dose of ethyl methanesulfonate at dose levels of 50, 100, and 200 mg/kg, 3 hr prior to necropsy. The results showed that sample cooling emerged as the predominant influence factor, whereas variations in other elements of the procedure (e.g., size of the liver piece sampled, time needed to process the liver tissue post-mortem, agarose temperature, or time of lysis) seem to be of little relevance. Storing of liver samples of up to 6 hr under cooled conditions did not cause an increase in tail intensity. In contrast, storing the tissue at room temperature, resulted in a considerable time-dependent increase in comet parameters.

True absorption and endogenous fecal excretion of manganese in relation to its dietary supply in growing rats.

A conventional balance study with 48 male weanling rats was conducted to determine true absorption and endogenous fecal excretion of manganese (Mn) in relation to dietary Mn supply, following the procedures of a previously adapted isotope dilution technique. After 10 d on a diet with 1.5 ppm Mn, eight animals each were assigned to diets containing 1.5, 4.5, 11.2, 35, 65, or 100 ppm Mn on a dry-matter basis. Three days later, each rat was given an intramuscular(54)Mn injection and kept on treatment for a balance period of 16 d.Apparent Mn absorption assessed for the final 8 d, averaged 8.6 µg/d without significant treatment effects, although Mn intake ranged from 18.6 to 1200 µg/d, in direct relation to dietary Mn concentrations. Mean fecal excretion of endogenous Mn for the six treatments was 0.9, 2.7, 7.4, 11.0, 16.3, and 17.7 µg/d, respectively. These values delineate the rates to which true absorption exceeded apparent rates. True absorption, as percent of Mn intake, averaged 28.7, 15.9, 11.7, 6.1, 3.4, and 2.0, respectively, as compared with mean values of 23.9, 10.9, 6.2, 3.4, 1.2, and 0.5 for percent apparent absorption. It was concluded that both true absorption and endogenous fecal excretion markedly responded to Mn nutrition and that the reduction in the efficiency of true absorption was quantitatively the most significant homeostatic response for maintaining stable Mn concentrations in body tissues.

Radioisotope-dilution technique for determining endogenous manganese in feces of the growing rat.

A conventional balance study with growing rats was conducted to evaluate experimental conditions for determining endogenous fecal manganese (Mn) excretion and, hence, true Mn absorption by the isotope-dilution technique. Thirty-four rats, with a mean initial live weight of 60 g, allotted to three groups of 8 animals and one group of 10 animals, were injected intramuscularly with a(54)Mn tracer dose and sacrificed after 4, 8, 12, and 16 d, respectively.In liver and serum, the specific radioactivity of Mn was the lowest among the tissues analyzed and its exponential rate of decrease over the period of d 4-16 was the highest. During the 8-d period, from d 9-16, apparent Mn absorption averaged 14.1% of intake (128.5 µg Mn/d). Assuming that the specific activity of Mn in liver of d 11 or, alternatively, in serum of d 16, was on the average representative of that of endogenous Mn in feces of d 9-16, it was computed that Mn of endogenous origin accounted for 9.0 and 9.3% of the total fecal excretion of the metal, and that true absorption amounted to 21.9 and 22.1% of Mn intake, respectively.