New Scale-up Technologies for Hydrogenation Reactions in Multipurpose Pharmaceutical Production Plants.

The classical scale-up approach for hydrogenation reaction processes usually includes numerous laboratory- and pilot-scale experiments. With a novel scale-up strategy, a significant number of these experiments may be replaced by modern computational simulations in combination with scale-down experiments. With only a few laboratory-scale experiments and information about the production-scale reactor, a chemical process model is developed.

Prospective evaluation of probabilistic dose-escalated IMRT in prostate cancer.

Background: Cure- and toxicity rates after intensity-modulated radiotherapy (IMRT) of prostate cancer are dose-and volume dependent. We prospectively studied the potential for organ at risk (OAR) sparing and compensation of tumor movement with the coverage probability (CovP) concept.

Patients And Methods: Twenty-eight prostate cancer patients (median age 70) with localized disease (cT1c-2c, N0, M0) and intermediate risk features (prostate-specific antigen [PSA] < 20, Gleason score ≤ 7b) were treated in a prospective study with the CovP concept.

Target miss using PTV-based IMRT compared to robust optimization via coverage probability concept in prostate cancer.

Cure- and toxicity rates of prostate IGRT can both be affected by ill-chosen planning target volume (PTV) margins. For dose-escalated prostate radiotherapy, we studied the potential for organ at risk (OAR) sparing and compensation of prostate motion with robust plan optimization using the coverage probability (CovP) concept compared to conventional PTV-based IMRT. We evaluated plan quality of CovP-plans for 27 intermediate risk prostate cancer patients treated in a prospective study (78 Gy/39 fractions).

MONOPOL - A traveling-wave magnetic neutron spin resonator for tailoring polarized neutron beams.

We report on first experimental tests of a neutron magnetic spin resonator at a very cold neutron beam port of the high flux reactor at the ILL Grenoble. When placed between two supermirror neutron polarizers and operated in a pulsed traveling-wave mode it allows to decouple its time- and wavelength-resolution and can therefore be used simultaneously as electronically tunable monochromator and fast beam chopper. As a first 'real' scientific application we intend its implementation in the PERC (p roton and e lectron r adiation c hannel) project related to high-precision experiments in neutron beta decay.

Organ Preservation in Rectal Cancer: The Patients' Perspective.

Organ preservation after a clinical complete response to radiochemotherapy is currently one of the most discussed topics in the management of rectal cancer. However, the patients' perspective has only been poorly studied so far. In this multicenter study, we examined 49 patients with locally advanced rectal cancer.

Long-term local control and survival after preoperative radiochemotherapy in combination with deep regional hyperthermia in locally advanced rectal cancer.

Purpose: The aim of this study was to evaluate the impact of deep regional hyperthermia on long-term local control and survival in locally advanced non-metastatic rectal cancer.

Methods: In total 103 patients with locally advanced non-metastatic rectal cancer were treated preoperatively with either neoadjuvant radiochemotherapy alone (n = 43) or the same treatment with additional deep regional hyperthermia (n = 60). The two groups were compared with respect to local control, overall survival (OS), disease-free survival (DFS), and distant metastases-free survival (DMFS).

A disease-specific enteral nutrition formula improves nutritional status and functional performance in patients with head and neck and esophageal cancer undergoing chemoradiotherapy: results of a randomized, controlled, multicenter trial.

Background: In patients with head and neck and esophageal tumors, nutritional status may deteriorate during concurrent chemoradiotherapy (CRT). The aim of this study was to investigate the influence of enteral nutrition enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on body composition and nutritional and functional status.

Methods: In a controlled, randomized, prospective, double-blind, multicenter study, 111 patients with head and neck and esophageal cancer undergoing concurrent CRT received either an enteral standard nutrition (control group) or disease-specific enteral nutrition Supportan®-containing EPA+DHA (experimental group) via percutaneous endoscopic gastrostomy.

Pathological complete response and sphincter-sparing surgery after neoadjuvant radiochemotherapy with regional hyperthermia for locally advanced rectal cancer compared with radiochemotherapy alone.

Purpose: To evaluate the influence of regional hyperthermia on rates of complete pathological response (pCR) and sphincter-sparing surgery in the context of an up-to-date radiochemotherapy protocol for locally advanced rectal cancer.

Methods: Between 2007 and 2010, 106 patients with locally advanced cancer of the middle and lower rectum were admitted to neoadjuvant radiochemotherapy either with (n = 61) or without (n = 45) regional hyperthermia. A retrospective comparison was performed between two groups: 45 patients received standard treatment consisting of 5040 cGy in 28 fractions to the pelvis and 5-fluorouracil (RCT group) and 61 patients received the same treatment in combination with regional hyperthermia (HRCT group).

Impact of radiotherapy, chemotherapy and surgery in multimodal treatment of locally advanced esophageal cancer.

Objectives: It was the aim of this study to assess our institutional experience with definitive chemoradiation (CRT) versus induction chemotherapy followed by CRT with or without surgery (C-CRT/S) in esophageal cancer.

Methods: We retrospectively analyzed 129 institutional patients with locally advanced esophageal cancer who had been treated by either CRT in analogy to the RTOG 8501 trial (n = 78) or C-CRT/S (n = 51).

Results: The median, 2- and 5-year overall survival (OS) of the entire collective was 17.

Radiation therapy for Gorham-Stout syndrome: results of a national patterns-of-care study and literature review.

Purpose: The German Cooperative Group on Radiotherapy for Benign Diseases conducted a national patterns-of-care study to investigate the value of radiation therapy (RT) in the management of Gorham-Stout syndrome.

Methods And Materials: In 2009 a structured questionnaire was circulated to 230 German RT institutions to assess information about the number of patients, the RT indication and technique, and the target volume definition, as well as accompanying treatments, outcome data, and early or late radiation toxicity.

Results: In November 2009 responses were available from 197 departments (85.

Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma.

Background: Whether it is possible to reduce the intensity of treatment in early (stage I or II) Hodgkin's lymphoma with a favorable prognosis remains unclear. We therefore conducted a multicenter, randomized trial comparing four treatment groups consisting of a combination chemotherapy regimen of two different intensities followed by involved-field radiation therapy at two different dose levels.

Methods: We randomly assigned 1370 patients with newly diagnosed early-stage Hodgkin's lymphoma with a favorable prognosis to one of four treatment groups: four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy of radiation therapy (group 1), four cycles of ABVD followed by 20 Gy of radiation therapy (group 2), two cycles of ABVD followed by 30 Gy of radiation therapy (group 3), or two cycles of ABVD followed by 20 Gy of radiation therapy (group 4).

Radiation therapy for treatment of pigmented villonodular synovitis: results of a national patterns of care study.

Purpose: The German Cooperative Group on Radiotherapy in Benign Diseases (GCG-BD) conducted a pattern-of-care study (PCS) to analyze the radiation therapy (RT) practice for pigmented villonodular synovitis (PVNS).

Methods And Materials: In 2007, a structured questionnaire to assess the number of patients, the pretreatments, the RT indication, technique, target volume concepts, outcome data, and possible early or late toxicity was circulated to 227 institutions.

Results: Until August 2008, a response was available from 189 institutions (83.

Reirradiation with alternating docetaxel-based chemotherapy for recurrent head and neck squamous cell carcinoma: update of a single-center prospective phase II protocol.

Purpose: To report follow-up data and results of a dose escalation within a prospective phase II protocol scheduling alternating chemoreirradiation for patients with unresectable locoregional recurrence of head and neck cancer after previous curative-intent radiotherapy.

Patients And Methods: Chemoreirradiation was initially performed in 27 patients by 40.0 Gy split-course reirradiation (re-RT) alternating with three cycles of docetaxel 50 mg/m(2) day 1 and cisplatin 15 mg/m(2) days 2-5 (first cohort).

Evidence-based radiation oncology: oesophagus.

Oesophageal cancer remains to be a therapeutic and diagnostic challenge in multidisciplinary oncology. Radiotherapy is a crucial component of most curative and palliative approaches for oesophageal cancer. Aim of this educational review is to summarize the available evidence and to define the role of radiation-based treatment options for oesophageal cancer.

High rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: results of a survey in EORTC institutes.

Objective: Examination of the rate of grade III or grade IV radiation dermatitis during treatment of head and neck cancer (HNC) with radiotherapy (RT) and concurrent cetuximab in EORTC centres.

Materials And Method: A questionnaire was sent to all members of the EORTC Radiation Oncology Group and Head and Neck Group (111 institutions) to evaluate the widespread use of cetuximab and radiotherapy in HNC and to estimate the frequency of grades III and IV skin reactions in the radiation portals associated with this protocol. Co-morbidities, RT schedules and co-medications were also recorded.

Model-independent, multimodality deformable image registration by local matching of anatomical features and minimization of elastic energy.

With respect to the demands of adaptive and 4D-radiotherapy applications, an algorithm is proposed for a fully automatic, multimodality deformable registration that follows the concept of translational relocation of regularly distributed image subvolumes governed by local anatomical features. Thereby, the problem of global deformable registration is broken down to multiple independent local registration steps which allows for straightforward parallelization of the algorithm. In a subsequent step, possible local misregistrations are corrected for by minimization of the elastic energy of the displacement field under consideration of image information.

Severe skin reaction secondary to concomitant radiotherapy plus cetuximab.

The therapeutic use of monoclonal antibodies against the epidermal growth factor receptor (EGFR) is specifically associated with dermatologic reactions of variable severity. Recent evidence suggests superiority of the EGFR inhibitor (EGFRI) cetuximab plus radiotherapy compared to radiotherapy alone in patients with squamous cell carcinoma of the head and neck. Although not documented in a study population, several reports indicate a possible overlap between radiation dermatitis and the EGFRI-induced skin rash.

External beam radiotherapy as postoperative treatment of diffuse pigmented villonodular synovitis.

Purpose: Diffuse pigmented villonodular synovitis is a rare proliferative disorder of synovial membranes with invasive and expansive growth patterns. Radical synovectomy is regarded as the treatment of choice. However, because of the high recurrence rates, additive treatment might be useful.

Paradoxical effects of hypoxia-mimicking divalent cobalt ions in human endothelial cells in vitro.

Divalent cobalt ions (Co2+) induce the expression of hypoxia responsive genes and are often used in cell biology to mimic hypoxia. In this in vitro study we compared the effects of hypoxia and Co2+ on human endothelial cells and examined processes that are stimulated in hypoxia in vivo (proliferation and angiogenesis). We analyzed the expression of the hypoxia-inducible factor-1alpha (HIF-1alpha) under different hypoxic conditions (3% and nearly 0% O2) and Co2+ -concentrations (0.

Divergent effects of GM-CSF and TGFbeta1 on bone marrow-derived macrophage arginase-1 activity, MCP-1 expression, and matrix metalloproteinase-12: a potential role during arteriogenesis.

Granulocyte/macrophage-colony stimulating factor (GM-CSF) and transforming growth factor (TGF)beta1 induce arteriogenesis in a nonischemic model of femoral artery ligation. Moreover, clinical trials demonstrated an improved collateralization after injection of bone marrow cells. In the present study, the expression of arteriogenic factors in bone marrow-derived macrophages (BMDM) was measured to verify the potential of these cells to influence collateral artery growth.

High levels of the molecular chaperone Mdg1/ERdj4 reflect the activation state of endothelial cells.

Mdg1/ERdj4, a mammalian chaperone that belongs to the HSP40 protein family, has been reported to be located in the endoplasmic reticulum (ER), is induced by ER stress, and protects ER stressed cells from apoptosis. Here we show that under normal physiological conditions, Mdg1/ERdj4 is expressed at various levels in the vasculature due to different activation states of the endothelium. To elucidate the stimuli that induce ER stress and thus upregulate Mdg1/ERdj4, we investigated the effect of several endothelium specific stressors on its expression.

Quantitative structure-transformation relationships of sulfonylurea herbicides.

Model development to predict transformation of sulfonylureas in different matrices was carried out using multiple linear regression. Descriptors for lipophilicity and molecular topology, as well as quantum chemical descriptors for energy, geometry, polarity, charges and reactivity using MOPAC with three different Hamiltonians, AM1, PM3 and MNDO, were calculated. In addition, experimental descriptors were measured and taken from the literature.