Eliminating the effects of reporting bias on risk perception.

Taking the public discourse on health risks due to aluminum in antiperspirants as an example, we conducted a randomized controlled study with repeated measurements to research how selective reporting of risk information affects risk perception and trust in risk information. First, the study varied the information scope that the experimental subjects received (selective vs. complete information). Selective information highlighted that a health risk is given. Considering the full range of studies, complete information is indicated the opposite. A second variation referred to the facticity of the hazardous agent mentioned in the risk information (a reference to either an actual or fictitious agent). Moreover, the selectively informed subjects received the complete information after the effects of the selective information were measured. Four risk perceptions constructs were chosen as dependent variables, differing on two dimensions (affective vs. cognitive and personal risk vs. risk for others). In addition, subjects´ trust in the given risk information was measured. The study reveals that presenting selective information amplifies risk perceptions. The effect was observed, irrespective of whether the hazardous agent mentioned in the risk information was actual or fictitious. When subjects who first received the selective information obtained the complete information, indicating no elevated risk, risk perceptions decreased. However, the analysis also indicates that corrective information (indicating no risk) is less trusted than selective information that points to health risks. Furthermore, proper toxicological understanding, i.e., taking into account the dose-response relationship, supports the effect of corrective information on risk perceptions.

Identifying content to improve risk assessment communications within the Risk Profile: Literature reviews and focus groups with expert and non-expert stakeholders.

OBJECTIVE: To improve consumer decision making, the results of risk assessments on food, feed, consumer products or chemicals need to be communicated not only to experts but also to non-expert audiences. The present study draws on evidence from literature reviews and focus groups with diverse stakeholders to identify content to integrate into an existing risk assessment communication (Risk Profile). METHODS: A combination of rapid literature reviews and focus groups with experts (risk assessors (n = 15), risk managers (n = 8)), and non-experts (general public (n = 18)) were used to identify content and strategies for including information about risk assessment results in the "Risk Profile" from the German Federal Institute for Risk Assessment. Feedback from initial focus groups was used to develop communication prototypes that informed subsequent feedback rounds in an iterative process. A final prototype was validated in usability tests with experts. RESULTS: Focus group feedback and suggestions from risk assessors were largely in line with findings from the literature. Risk managers and lay persons offered similar suggestions on how to improve the existing communication of risk assessment results (e.g., including more explanatory detail, reporting probabilities for individual health impairments, and specifying risks for subgroups in additional sections). Risk managers found information about quality of evidence important to communicate, whereas people from the general public found this information less relevant. Participants from lower educational backgrounds had difficulties understanding the purpose of risk assessments. User tests found that the final prototype was appropriate and feasible to implement by risk assessors. CONCLUSION: An iterative and evidence-based process was used to develop content to improve the communication of risk assessments to the general public while being feasible to use by risk assessors. Remaining challenges include how to communicate dose-response relationships and standardise quality of evidence ratings across disciplines.

[Risk communication of the Federal Institute for Risk Assessment during a food-related outbreak]. / Risikokommunikation des Bundesinstituts für Risikobewertung bei einem lebensmittelbedingten Ausbruch.

Information about and explanation of risks as well as the initiation of behavioral changes and preventive actions are core tasks of risk communication. During the EHEC/HUS outbreak in spring 2011, the governmental agencies responsible for risk communication mainly focused on these tasks. In general, risk communication is understood as a continuous, long-term process that aims at an adequate handling of risks. In contrast, crisis communication is focused rather on an acute event and aims at timely information and behavioral measures. During the EHEC/HUS outbreak, risk communication partly changed over to crisis communication. The risk communication activities of the Federal Institute for Risk Assessment (Bundesinstitüt für Risikobewertung, BfR) during the EHEC/HUS outbreak are presented here. The results of a representative survey that was conducted in Germany shortly after the outbreak show details of the success of these risk communication activities. Finally, the necessity of communication about scientific uncertainty is addressed and new ways in risk communication with regard to new media are highlighted.

Micrometre resolution of a charge integrating microstrip detector with single photon sensitivity.

A synchrotron beam has been used to test the spatial resolution of a single-photon-resolving integrating readout-chip coupled to a 320 µm-thick silicon strip sensor with a dedicated readout system. Charge interpolation methods have yielded a spatial resolution of σ(x) ≃ 1.8 µm for a 20 µm-pitch strip.

[Progress in undergraduate and postgraduate education in abdominal ultrasonography at German university hospitals in 1999-2009]. / Aus- und Weiterbildungssituation in der Abdomensonografie an deutschen Universitätskliniken--Vergleich 1999-2009.

AIM: The aim of this study was to assess the current state of undergraduate and postgraduate education in abdominal ultrasonography at German university hospitals and to compare these findings with data from 1999. METHODS: A survey, encompassing questions related to technical equipment, undergraduate education, graduate education and quality assurance, was conducted at all 36 gastroenterological departments of university hospitals in Germany. The response rate was 86 %. RESULTS: Currently, there is an average of four dedicated ultrasound units for abdominal ultrasonography per department. Two percent are basic units, 12 % are middle-class and 86 % are high-end units. Compared to 1999 there has been an improvement in the quality of ultrasound units but no increase in number; the percentage of high-end units has considerably increased. All departments offer undergraduate training in abdominal ultrasonography. On average, about 100 students per semester take part in training programmes. Ten years ago only 86 % of hospitals provided undergraduate training, for an average of 55 students per semester. Postgraduate training is offered full-time in 94 % of hospitals (1999: 77 %) over a mean time span of 6.1 months (1999: 4.3 months). In 2009a mean of 4.7 physicians per department underwent ultrasonography training, down from 5.6 physicians per department in 1999. CONCLUSION: Over the ten-year observation period, the quality of dedicated ultrasonography equipment for abdominal ultrasonography in the gastroenterological departments of German university hospitals has improved considerably, while the quality of postgraduate education has improved only slightly. In addition, there was improvement in undergraduate ultrasonography training.

[Research activity in abdominal ultrasonography in German university departments of gastroenterology - comparison between 1999 and 2009]. / Forschungssituation in der Abdomensonografie in den gastroenterologischen Abteilungen der Universitätskliniken in der Bundesrepublik Deutschland - Vergleich 1999 - 2009.

AIM: The aim of this study was to generate an overview of the current research situation in abdominal ultrasonography conducted by gasteroenterology departments of German university hospitals and to compare this situation with data from 1999. METHODS: A survey was sent to all 36 German university hospitals encompassing information on research topics, number of research projects and publications, grants, and support by manufacturers of ultrasonography units. The response rate was 86 %. RESULTS: 74 % of gastroenterological departments had 113 ongoing research projects during the enquiry period - on average 3.6 projects per departement. Of these projects 43 % were clinical research, 11 % technical studies, 13 % various topics and 33 % studies with ultrasound contrast enhancers. Ten years ago 80 % of gastroenterological departments had research projects - on average 3.5 projects per department. There was no significant difference in the number of publications between the two enquiry periods. The percentage of publications in English had increased considerably from 57 % (1999) to 78 % (2009). Regarding scientific grants there was no relevant difference during the observed time spans. A total of 32 % (1999: 26 %) of departments receive external funding in addition to their regular budgets. Forty-five percent (1999: 31 %) receive support from manufacturers in the form of hard- and software for application studies. CONCLUSION: Regrettably the research situation in abdominal ultrasonography has not improved considerably during the observed time span. As already stated in 1999, the urgent need for improved research funding for what is the most widely applied image modality still remains an ongoing concern.

Cluster-randomized controlled trial of dissemination strategies of an online quality improvement programme for alcohol-related disorders.

AIMS: This project investigated different dissemination strategies of an online quality improvement programme for alcohol-related disorders into routine care in South Baden and South Württemberg in Germany. METHODS: In a cluster-randomized controlled trial, 112 general practices were randomized into three groups. The first group (n = 43) received access to the online system and a training programme for the general practitioners (GPs). The second group (n = 42) additionally received education for the whole practice team. The third group (n = 27) acted as control and received only access to the online system. RESULTS: Two thousand six hundred and forty-seven practitioners were asked to take part in the study, and it was possible to randomize 112 (4%) practices. There were no significant differences concerning the use of the system between the groups: 41.9% of the GPs in the first group, 42.9% in the second group and 44.4% in the control group used the system. In terms of only the system users, 55.6% of the GPs in the first group, 33.3% in the second group and 8.3% in the control group used the system six times or more (P = 0.019). Diagnostic assessments made by the GPs in the groups differed substantially: 72.2% of diagnoses in the first group were correct, while this figure lay at 69.7% in the second group and 36.4% in the control group (P = 0.034). CONCLUSIONS: No effect of the additional training on the primary outcome (acceptance) was identified, but on two of the secondary outcomes. Further cost-effectiveness studies should investigate whether the effort involved in providing training additionally to the system is justifiable. The study is registered at ClinicalTrials.gov: NCT00314067. This article conforms to the guidelines in the Consolidated Standards of Reporting Trials (CONSORT) statement (Moher et al., 2001; Campbell et al., 2004).

Novel molecular profiles of endometrial cancer-new light through old windows.

Endometrial carcinoma (EC) is the most common gynecological malignancy in the western world. A widely accepted dualistic model, which has been established on a morphological basis, differentiates EC into two broad categories: Type I oestrogen-dependent adenocarcinoma with an endometrioid morphology and Type II non-oestrogen-dependent EC with a serous papillary or clear cell morphology. Molecular genetic evidence indicates that endometrial carcinoma, as described in other malignancies, likely develops as the result of a stepwise accumulation of alterations in cellular regulatory pathways, such as oncogene activation and tumor suppressor gene inactivation, which lead to dysfunctional cell growth. These molecular alterations appear to be specific in Type I and Type II cancers. In type I endometrioid endometrial cancer, PTEN gene silencing in conjunction with defects in DNA mismatch repair genes, as evidenced by the microsatellite instability phenotype, or mutations in the K-ras and/or beta-catenin genes, are recognized major alterations, which define the progression of the normal endometrium to hyperplasia, to endometrial intraepithelial neoplasia, and then on to carcinoma. In contrast, Type II cancers show mutations of TP53 and Her-2/neu and seem to arise from a background of atrophic endometrium. Nevertheless, despite the great effort made to establish a molecularly-based histological classification, the following issues must still be clarified: what triggers the tumor cells to invade the myometrium and what causes vascular or lymphatic dissemination, finally culminating in metastasis? RUNX1, a transcription factor, was recently identified as one of the most highly over-expressed genes in a microarray study of invasive endometrial carcinoma. Another candidate gene, which may be associated with an initial switch to myometrial infiltration, is the transcription factor ETV5/ERM. These studies, as well as those conducted for other genes possibly involved in the mitotic checkpoint as a major mechanism of carcinogenesis in non-endometrioid endometrial cancer, could help in understanding the differences in the biology and the clinical outcome among histological types.

Development and investigation of a pollution control pit for treatment of stormwater from metal roofs and traffic areas.

Source control by on-site retention and infiltration of stormwater is a sustainable and proven alternative to classical drainage methods. Unfortunately, sedimentary particles and pollutants from drained surfaces cause clogging and endanger soil and groundwater during long-term operation of infiltration devices. German water authorities recommend the use of infiltration devices, such as swales or swale-trench-systems. Direct infiltration by underground facilities, such as pipes, trenches or sinks, without pretreatment of runoff is generally not permitted. Problems occur with runoff from metal roofs, traffic areas and industrial sites. However, due to site limitations, underground systems are often the only feasible option. To overcome this situation, a pollution control pit was developed with a hydrodynamic separator and a multistage filter made of coated porous concrete. The system treats runoff at source and protects soil, groundwater and receiving waterways. Typically, more than 90% of the pollutants such as sedimentary particles, hydrocarbons and heavy metals can be removed. Filters have been developed to treat even higher polluted stormwater loads from metal roofs and industrial sites. The treatment process is based on sedimentation, filtration, adsorption and chemical precipitation. Sediments are trapped in a special chamber within the pit and can be removed easily. Other pollutants are captured in the concrete filter upstream of the sediment separator chamber. Filters can be easily replaced.

Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging.

Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening.

Sustained silver-releasing dressing in the treatment of diabetic foot ulcers.

This study investigated the clinical performance and safety of a sustained silver-releasing foam dressing, Contreet Foam, in the treatment of diabetic foot ulcers. Twenty-seven patients with diabetic foot ulcers of grade I or II (Wagner's classification) were followed for six weeks: one week run-in using Biatain dressings, four weeks' treatment with Contreet dressings. Four ulcers healed during the four-week treatment with Contreet 56% in average. Contreet Foam showed good exudate management properties and was considered easy to use. Only two infections occurred showed that all six of the non-study ulcers developed an infection during the study. All ulcers (study ulcers as well as non-study ulcers) were treated according to good practice of diabetic wound care. There were no directions for the treatment of secondary wounds. No device-related adverse events were observed. This study demonstrated that Contreet Foam is safe and easy to use and effectively supports healing and good wound progress of diabetic foot ulcers.

Safety and performance of a new non-adhesive foam dressing for the treatment of diabetic foot ulcers.

OBJECTIVE: This study aimed to document the safety and performance of a new non-adhesive foam dressing (Biatain Non-adhesive Dressing, Coloplast A/S) in the treatment of established foot ulcers in patients with diabetes. METHOD: This was an open non-comparative prospective study. Participants had an ankle brachial pressure index score of over 0.4 (neuro-ischaemic) and an ulcer bigger than 1 cm2 and less than 8 cm2 in any direction. The treatment period was six weeks. RESULTS: Thirty-five out of 37 patients completed the study. The mean wound area reduced from 5.4 cm2 to 2.5 cm2. Relative wound area reduced from 100% at baseline to 40% at week 6. 'Wearing comfort' improved throughout the study (p = 0.039). Maceration remained stable or improved. None of the four reported adverse events were device related. CONCLUSION: This study demonstrates that treatment of diabetic foot ulcers with Biatain Non-adhesive Dressing results in considerable wound area reduction and prevents any deterioration in maceration. The dressing is safe and effective in the management of these ulcers.

Comparison of intravenous coronary angiography using synchrotron radiation with selective coronary angiography.

Intravenous coronary angiography with synchrotron radiation is a novel and minimally invasive technique for coronary imaging. At the Hamburger Synchrotronstrahlungslabor HASYLAB at DESY, a dedicated angiography system has been developed, which has been shown to provide detailed images of coronary artery segments. For each scan, two monochromatic X-ray images below and above the K-edge of iodine were recorded simultaneously. The two images were subtracted logarithmically to produce a maximal contrast enhancement of the iodine. To date, the procedure has been carried out on 379 outpatients. No complications occurred during or after the angiographic procedure, and hospitalization was not required in any subject. The acceptance by patient is extremely high. Five outside reviewers, blinded as to the clinical data or prior angiographic interpretation, reviewed the images for the presence or absence of 70% or more occlusion of a vessel. They reached a sensitivity of 79% and a specificity of 99%. The study has demonstrated that the synchrotron method has satisfactory sensitivity and very high specificity for severe stenoses. The new method has several advantages over magnetic resonance imaging (MRI), electron beam computed tomography (EBCT), and multi-slice computed tomography (MSCT). Neither vascular calcification (CT) nor the presence of metal stents (MRI) impairs the evaluation of perfusion of segments of the coronary arteries. Furthermore, the spatial resolution is three or four times higher using synchrotron angiography, and problems due to respiratory motion are eliminated.

Lysine and polyamines are substrates for transglutamination of Rho by the Bordetella dermonecrotic toxin.

Bordetella dermonecrotic toxin (DNT) catalyzes the transglutamination of glutamine-63/61 of Rho GTPases, thereby constitutively activating Rho proteins. Here we identified second substrates for transglutamination of RhoA by DNT. The enzymatically active fragment of DNT (residues 1136 to 1451, DeltaDNT) induced the incorporation of L-[(14)C]lysine in RhoA in a concentration-dependent manner. Also, Rac and Cdc42, but not Ras, were transglutaminated with lysine by DeltaDNT. Transglutamination of the GTPase with L-lysine inhibited intrinsic and Rho-GAP-stimulated GTP hydrolysis of RhoA. In contrast to lysine, treatment of RhoA with alanine, arginine, and glutamine were not able to substitute for lysine in the transglutamination reaction. DNT increased the incorporation of L-[(14)C]lysine into embryonic bovine lung cells. Microinjection of GST-RhoA together with the enzymatically active DNT fragment into Xenopus oocytes, subsequent affinity purification of modified GST-RhoA, and mass spectrometry identified attachment of putrescine or spermidine at glutamine-63 of RhoA. A comparison of putrescine, spermidine, and lysine as substrates for DNT-induced transglutamination of RhoA revealed that lysine is a preferred second substrate at least in vitro.

A new concept of a multidisciplinary wound healing center and a national expert function of wound healing.

HYPOTHESIS: An independent, multidisciplinary wound healing center in an accepted national expert function of wound healing is the optimal way to improve prophylaxis and treatment of patients with problem wounds. DESIGN: A clinical perspective analysis. SETTING: An independent, multidisciplinary wound healing center focusing on all types of problem wounds, organized as a university hospital department, and integrated in an expert function in the national health care organization of Denmark. PATIENTS AND METHODS: Patients with all types of problem wounds referred to and treated in the center during the first years of its existence provided a model for a new multidisciplinary structure for treatment of wound patients in the health care system. RESULTS: During the first 3 years of the fully functioning wound healing center, a total of 23 802 patient consultations were performed in the outpatient clinic, and 1014 patients with problem wounds were hospitalized in the inpatient ward. The surgical concept of the center has resulted in improved healing rates in patients with leg ulcers and decreased rates of major amputations. The outpatient function has resulted in a decrease in the number of patients transported in beds to the center. This structure provides better opportunities for basic and clinical research as well as for establishing expert education for all types of health care personnel. The center's structure has been the background for establishing an expert function in wound healing, allowing the wound healing area area to be fully integrated in the Danish National Health Care System. Overall, the concept and structure of the center have enhanced the knowledge and understanding of wound problems and increased the status of wound healing and patient care. CONCLUSIONS: Establishing multidisciplinary centers integrated into an accepted national expert function of wound healing is an optimal way to improve the clinical outcome of prophylaxis and treatment of all types of problem wounds. This model, with minor adjustments, may be applicable for both industrialized and developing countries.

Intravenous coronary angiography using synchrotron radiation: technical description and preliminary results.

BACKGROUND: Standard coronary angiography requires an arterial access and catheters; intravenous coronary angiography may image coronary arteries noninvasively and without catheters. The aim of this study was the assessment of the diagnostic accuracy of intravenous coronary angiography validated by selective coronary angiography. METHODS: Seventy outpatients (80% males, mean age 62 +/- 8 years) underwent both standard and intravenous coronary angiography after a previous coronary intervention. Intravenous coronary angiography was performed within 6 weeks before or after selective coronary angiography. Two different projections were used to obtain 6-8 sequences per patient. Images were taken after injection of the contrast agent into the brachial vein or into the superior vena cava. During image acquisition, patients were moved through the scanning beam on a special chair. Thereafter, images were evaluated and compared to selective coronary angiograms for the following criteria: no stenosis, subsignificant stenosis (< 70%), significant stenosis (> or = 70%), and occlusion. RESULTS: One hundred eighty-seven target vessels were analyzed. In 50 target vessels one or more stents had been implanted. Seventeen target vessels were not analyzable due to inadequate image quality. The sensitivity of intravenous coronary angiography for the detection of lesions was 80% and the specificity was 95%. The sensitivity for the detection of significant lesions in the left anterior descending coronary artery was 84% (specificity 93%), in the left circumflex coronary artery 67% (specificity 90%), in the right coronary artery 85% (specificity 97%), and in bypass grafts 85% (specificity 97%). No complications were observed. CONCLUSIONS: Intravenous coronary angiography is efficacious and safe and allows quantification of lesions of the coronary arteries and of bypass vessels. Further advances in image processing are needed to improve sensitivity especially in the left circumflex coronary artery.

Sequestration of biological reactive intermediates by trapping as covalent enzyme-intermediate complex.

One important class of biological reactive intermediates arising in the course of human xenobiotic metabolism are arene and alkene oxides. The major safeguard against the potential genotoxic effects of these compounds is the microsomal epoxide hydrolase (mEH). This enzyme has a broad substrate specificity but--on the first sight--seems to be inadequately suited for this protection task due to its low turnover number with most of its substrates. The recent progress in the understanding of the mechanism of enzymatic epoxide hydrolysis has shed new light on this apparent dilemma: Epoxide hydrolases convert their substrates via the intermediate formation of a covalent enzyme-substrate complex, and it has been shown that the formation of the intermediate proceeds by orders of magnitudes faster than the subsequent hydrolysis, i.e. the formation of the terminal product. Thus, the enzyme acts like a molecular sponge by binding and inactivating the dangerous metabolite very fast while the subsequent product release is considerably slower, and quantification of the latter heavily underestimates the speed of detoxification. Usually, the slow enzyme regeneration does not pose a problem, since the mEH is highly abundant in human liver, the organ with the highest capacity to metabolically generate epoxides. Computer simulation provides evidence that the high amount of mEH enzyme is crucial for the control of the steady-state level of a substrate epoxide and can keep it extremely low. Once the mEH is titrated out under conditions of extraordinarily high epoxide concentration, the epoxide steady-state level steeply rises, leading to a sudden burst of the genotoxic effect. This prediction of the computer simulation is in perfect agreement with our experimental work. V79 Chinese Hamster cells that we have genetically engineered to express human mEH at about the same level as that observed in human liver are well protected from any measurable genotoxic effect of the model compound styrene oxide (STO) up to an apparent threshold level of 100 microM in the cell culture medium. In V79 cells that do not express mEH, STO triggers the formation of DNA strand breaks in a dose-dependent manner with no apparent threshold. Above 100 microM, the genotoxic effect of STO in the mEH-expressing cell line parallels the one in the parental cell line.

Charge order in NaV2O5 studied by EPR

We present angular dependent EPR measurements in NaV2O5 at X-band frequencies in the temperature range 4.2/=100 K, is followed by zigzag charge-order fluctuations which become long range and static below T(SP) = 34 K.

Dendritic cells lose ability to present protein antigen after stimulating antigen-specific T cell responses, despite upregulation of MHC class II expression.

Immature dendritic cells (DC) take up, process and present protein antigens; mature DC are specialized for stimulating primary T cell responses with increased expression of MHC class II and co-stimulatory molecules, but are incapable of processing and presenting soluble protein. The current study examined whether maturation of DC is triggered by T cell recognition of antigens presented by immature DC. Human DC derived from CD34+ progenitor cells by culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-6 (IL-6) in serum-free medium could prime naive CD4+ T cells to keyhole limpet hemocyanin (KLH) and ovalbumin (OVA). The cultured DC retained the ability to prime T cells to native protein for at least 15 days. To test for changes in DC function after participation in an immune response, DC were co-cultured with either allogeneic or autologous CD4+ T cells. DC co-cultured with autologous T cells retained the ability to prime T cells to intact protein antigens. By contrast, DC which had previously stimulated an allogeneic T cell response lost ability to prime T cells to soluble proteins. However, such <> induced a MLR and stimulated peptide-specific primary CD4+ T cell responses. This indicated that <> did not die or lose the ability to prime, but lost the ability to process and present subsequent antigens. Following participation in T cell activation, DC increased surface expression of MHC class II, co-stimulatory molecules CD40 and B7.2, and the intercellular adhesion molecule-1 (ICAM-1). In addition, our data suggest that interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) are involved in this T cell-mediated DC maturation.