The Global Atmosphere-aerosol Model ICON-A-HAM2.3-Initial Model Evaluation and Effects of Radiation Balance Tuning on Aerosol Optical Thickness.

The Hamburg Aerosol Module version 2.3 (HAM2.3) from the ECHAM6.3-HAM2.3 global atmosphere-aerosol model is coupled to the recently developed icosahedral nonhydrostatic ICON-A (icon-aes-1.3.00) global atmosphere model to yield the new ICON-A-HAM2.3 atmosphere-aerosol model. The ICON-A and ECHAM6.3 host models use different dynamical cores, parameterizations of vertical mixing due to sub-grid scale turbulence, and parameter settings for radiation balance tuning. Here, we study the role of the different host models for simulated aerosol optical thickness (AOT) and evaluate impacts of using HAM2.3 and the ECHAM6-HAM2.3 two-moment cloud microphysics scheme on several meteorological variables. Sensitivity runs show that a positive AOT bias over the subtropical oceans is remedied in ICON-A-HAM2.3 because of a different default setting of a parameter in the moist convection parameterization of the host models. The global mean AOT is biased low compared to MODIS satellite instrument retrievals in ICON-A-HAM2.3 and ECHAM6.3-HAM2.3, but the bias is larger in ICON-A-HAM2.3 because negative AOT biases over the Amazon, the African rain forest, and the northern Indian Ocean are no longer compensated by high biases over the sub-tropical oceans. ICON-A-HAM2.3 shows a moderate improvement with respect to AOT observations at AERONET sites. A multivariable bias score combining biases of several meteorological variables into a single number is larger in ICON-A-HAM2.3 compared to standard ICON-A and standard ECHAM6.3. In the tropics, this multivariable bias is of similar magnitude in ICON-A-HAM2.3 and in ECHAM6.3-HAM2.3. In the extra-tropics, a smaller multivariable bias is found for ICON-A-HAM2.3 than for ECHAM6.3-HAM2.3.

Bounding Global Aerosol Radiative Forcing of Climate Change.

Aerosols interact with radiation and clouds. Substantial progress made over the past 40 years in observing, understanding, and modeling these processes helped quantify the imbalance in the Earth's radiation budget caused by anthropogenic aerosols, called aerosol radiative forcing, but uncertainties remain large. This review provides a new range of aerosol radiative forcing over the industrial era based on multiple, traceable, and arguable lines of evidence, including modeling approaches, theoretical considerations, and observations. Improved understanding of aerosol absorption and the causes of trends in surface radiative fluxes constrain the forcing from aerosol-radiation interactions. A robust theoretical foundation and convincing evidence constrain the forcing caused by aerosol-driven increases in liquid cloud droplet number concentration. However, the influence of anthropogenic aerosols on cloud liquid water content and cloud fraction is less clear, and the influence on mixed-phase and ice clouds remains poorly constrained. Observed changes in surface temperature and radiative fluxes provide additional constraints. These multiple lines of evidence lead to a 68% confidence interval for the total aerosol effective radiative forcing of -1.6 to -0.6 W m-2, or -2.0 to -0.4 W m-2 with a 90% likelihood. Those intervals are of similar width to the last Intergovernmental Panel on Climate Change assessment but shifted toward more negative values. The uncertainty will narrow in the future by continuing to critically combine multiple lines of evidence, especially those addressing industrial-era changes in aerosol sources and aerosol effects on liquid cloud amount and on ice clouds.

Opposite Aerosol Index-Cloud Droplet Effective Radius Correlations Over Major Industrial Regions and Their Adjacent Oceans.

The Moderate Resolution Imaging Spectroradiometer (MODIS) C6 L3 and the European Centre for Medium-Range Weather Forecasts (ECMWF) ERA-Interim reanalysis data from 2003 to 2016 are employed to study aerosol-cloud correlations over three industrial regions and their adjacent oceans, as well as explore the impact of meteorological conditions on the correlations. The analysis focusing on liquid and single-layer clouds indicates an opposite aerosol-cloud correlation between land and ocean; namely, cloud effective radius is positively correlated with aerosol index over industrial regions (positive slopes), but negatively correlated over their adjacent oceans (negative slopes), for a quasi-constant liquid water path. The positive slopes are relatively large under low lower-tropospheric stability (LTS; weakly stable condition), but much weaker or even become negative under high LTS (stable conditions) and high liquid water path. The occurrence frequency of cloud top height (CTH) and LTS suggests that positive correlations are more likely corresponding to relatively high CTH and low LTS, while negative to low CTH and high LTS.

Establishment of the Certification System "Gynaecological Dysplasia" in Germany.

Gynaecological cancer centres have been established nationwide in Germany since 2008 according to the certification system of the German Cancer Society (Deutsche Krebsgesellschaft e. V. [DKG]) and the German Society for Gynaecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe e. V. [DGGG]). However, patient access to the certified gynaecological cancer centres is currently only possible through direct referrals. A longitudinal structure with the corresponding long-term documentation of both the high-grade precursors as well as the cancers does not exist as yet. According to the aims of the National Cancer Plan, a corresponding structure for the cancer entity "cervix carcinoma" should be established. The foundations for such a structure are appropriate diagnostic units that are responsible, after nationwide screening, for clarification according to guideline-conform principles. On the basis of the vote of the certification commission for gynaecological cancer centres under the chairmanship of the DKG, the Working Group for Gynaecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie e. V. [AGO]), the Committee on Cervical Pathology and Colposcopy (Arbeitsgemeinschaft Zervixpathologie & Kolposkopie [AG-CPC]) and the DGGG the certification system for gynaecological dysplasia has been established. As a general principle, a distinction is made between the certification of a consulting practice for gynaecological dysplasia and a gynaecological dysplasia facility in order to integrate both outpatient and inpatient health-care facilities into the certification system. In analogy to the further catalogue of requirements from the DKG, quantitative and qualitative minimum numbers are demanded. Furthermore, the requirements of the certification process include a summary of patient information, the applied guidelines, continuing and further training, interdisciplinary cooperation in tumour boards, contents or, respectively, procedure descriptions for consulting practices and the trial participations. Central components of the questionnaire are quality indicators that can be used as specific and measurable elements to evaluate the quality of treatment. After successful pilot certification, finalisation of the updated version of the questionnaire and a completed specialist auditor training course for the certification of gynaecological dysplasia, it will be possible to establish a nationwide treatment system for dysplasia within certified structures.

Explanation and Use of the Rio 2011 Colposcopy Nomenclature of the IFCPC (International Federation for Cervical Pathology and Colposcopy): Comments on the general colposcopic assessment of the uterine cervix: adequate/inadequate; squamocolumnar junction; transformation zone.

In July 2012 the IFCPC adopted a revised terminology for colposcopic examinations of the uterine cervix. In 2012, the Boards of the Arbeitsgemeinschaft Kolposkopie (AGK - Austrian Society of Colposcopy), the Arbeitsgemeinschaft für Kolposkopie und Zervixpathologie (AGKOL - Swiss Society of Colposcopy and Cervical Pathology) and the Arbeitsgemeinschaft für Kolposkopie und Zervixpathologie (AGCPC - German Society of Colposcopy and Cervical Pathology) accepted the validity of the 2011 IFCPC nomenclature and recommended its use in general clinical practice across German-speaking countries. The revised nomenclature was devised so that examiners can evaluate colposcopic criteria according to a specific scheme. At the start of the examination, the examiner must assess whether the colposcopy is representative or not. 1. Can the examination be classed as adequate or inadequate (reasons must be given)? 2. How would you describe the visibility of the squamocolumnar junction and categorize the transformation zone? Below we discuss some aspects of this general assessment as outlined in the nomenclature which were found to require further clarification for general practice.

Explanation and Use of the Colposcopy Terminology of the IFCPC (International Federation for Cervical Pathology and Colposcopy) Rio 2011.

In July 2012 a revised terminology on colposcopic examinations of the cervix uteri was adopted by IFCPC. Central aspect is a description of characteristics that should aid in the definition of the disease entity cervix uteri. The nomenclature is built up in such a way that the examiner can evaluate colposcopic criteria according to a specific scheme. Firstly it is assessed whether the colposcopy is representative. Then it should be clarified whether or not the findings are normal. If the findings are not normal but rather abnormal the severity of the lesion is classified according to the so-called grade 1 (minor change) and grade 2 findings (major change). Specific abnormal findings such as leukoplakia, erosion and Lugol's finding are also not defined at this point. Characteristics suspicious for an invasion are described separately, in particular, atypical vessel patterns are mentioned here. As already held in the previous revised nomenclature (Barcelona), various findings are described in a last group: congenital transformation zones (CTZ), congenital anomalies, condylomas (papillomas), endometriosis, polyps (ectocervical, endocervical), inflammation, stenosis, postoperative changes (scarred portio, vaginal stump).

Docetaxel and carboplatin as first-line chemotherapy in patients with advanced gynecological tumors. A phase I/II trial of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-OVAR) Ovarian Cancer Study Group.

OBJECTIVES: We performed a phase I-II study in patients with ovarian and other gynecological cancers to determine the dose-limiting toxicities, maximum tolerated dose (MTD) and efficacy of docetaxel/carboplatin. METHODS: Thirty patients were treated in three cohorts with carboplatin (AUC 5) and escalating docetaxel (60, 75 and 90 mg/m2), administered intravenously on day 1, repeated every 3 weeks. Premedication consisted of 16 mg dexamethasone per os on day -1, and +1 and 4 mg intravenously before docetaxel. RESULTS: A total of 6, 11 and 12 patients were eligible and treated on dose levels 1, 2 and 3, respectively. At docetaxel 90 mg/m2, febrile and prolonged neutropenia were dose-limiting, and 75 mg/m2 with carboplatin AUC 5 was considered the MTD. Prolonged neutropenia occurred in two, four and nine patients of dose levels 1-3, respectively, and febrile neutropenia in 2, 1, and 2 patients of dose level 1-3. Thrombocytopenia grade 4 was observed in one patient of dose level 1. Non-hematological toxicity including neuropathy was usually mild across all dose levels. Overall response rate was 73%. Median time to progression was 18.0 months, and median overall survival will exceed 24.4 months. CONCLUSIONS: Docetaxel/carboplatin can be safely administered to patients with gynecological cancer despite substantial myelotoxicity and appears to be active in the treatment of ovarian cancer. Low neurotoxicity offers an option for comparison with paclitaxel-containing regimens.

Second-line carboplatin and gemcitabine in platinum sensitive ovarian cancer--a dose-finding study by the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) Ovarian Cancer Study Group.

BACKGROUND: Despite the progress that has been achieved in the last years, recurrence rates in ovarian cancer patients are still considerably high and the majority of patients ultimately become candidates for second-line treatment. Carboplatin reinduction is a broadly adopted regimen in patients with recurrences occurring six months or later after first-line treatment. Gemcitabine is among the candidates as combination partner in second-line regimens. PATIENTS AND METHODS: We performed a study with escalating doses of gemcitabine combined with carboplatin in 26 platinum-pretreated patients with recurrent ovarian cancer and a treatment-free interval of 6+ months. Dose-limiting toxicity (DLT) and a maximum tolerable dose (MTD) recommendable for further trials was evaluated. RESULTS: The DLT was myelosuppression, mainly thrombocytopenia. No dose limiting non-hematological toxicities were observed. The MTD of gemcitabine was 1,000 mg/m2 given on days 1 + 8 of a three-week schedule combined with carboplatin AUC 4 given on day 1. The majority of evaluable patients showed an objective response (62.5%), and median progression-free and overall survival were 10 and 18+ months, respectively. CONCLUSION: Gemcitabine-carboplatin given according to the MTD is well tolerated and active against recurrent platinum-sensitive disease. A randomized trial comparing carboplatin with or without gemcitabine in platinum-sensitive ovarian cancer has already been initiated.

Cervical intraepithelial neoplasia--biopsy methods as AIDS for diagnosis and therapy.

Between 1977 and 1995, a total of 1610 patients were admitted to hospital with Pap III, IIID, IVa or IVb. The results of 1182 conisations with cervical abrasion and 428 ectocervical surface scrapings with cervical abrasion were evaluated. The percentage of findings of (CIN II was 35.2% for all cases and 23.3% for conisation alone. No atypical findings or CIN I was seen in 13.9% of all conisation cases. The introduction of a second biopsy method (ectocervical surface scraping (ESS) in 1985 resulted in the reduction of cases with a positive histological finding for conisations of (CIN I from 17.7% (1977-1984, n = 468) to 11.3% (1985-1995, n = 714). Evaluation of combined PA and punch biopsy from the ectocervix assisted by colposcopy was performed in 130 cases. Histological correspondence between the methods was seen in 44.6% of the cases. In 22.3% of the patients the highest CIN degree was seen in the biopsy material obtained under colposcopic observation, while in 33.1% of the cases the highest degree of dysplasia was seen in the material obtained by ectocervical surface scraping. Conisation as the sole diagnostic tool can be replaced by combined and simplified biopsy techniques without prejudice to safety. If only PA is performed, the possibility cannot be ruled out that in individual cases an early-stage invasive cervical carcinoma may be overlooked. Conisation performed without evidence of atypical epithelial structures or only CIN I findings must be regarded as over-treatment. For all CIN III cases, however, conisation remains the most important form of therapy.

[Is there an increase of serum antisperm antibodies following surgery in the cervical transformation zone for cervical intraepithelial neoplasia (CIN)?]. / Führen aufgrund einer zervikalen intraepithelialen Neoplasie (CIN) durchgeführte Operationen an der zervikalen Transformationszone zu einem Anstieg humoraler Antispermatozoen-Antikörper?

OBJECTIVE: This prospective controlled study was performed to investigate whether operative procedures of the uterine cervix lead to a change in the titre of humoral antispermatozoal antibodies. MATERIAL AND METHODS: Humoral antispermatozoal antibodies were measured using an ELISA in 15 patients undergoing cervical scraping, 20 having conisation, 10 having a loop excision before and at least 3 months after surgery as well as in 10 fertile women as a control group. RESULTS: There were no significant differences in age between groups, in the distribution of initial and final levels of humoral antispermatozoal antibodies (IgG, IgA), and no significant change of the antibody titres (pre- and postoperative) within the individual groups. CONCLUSIONS: In patients of fertile age, the formation of humoral isoantibodies does not have to be taken into account in selecting the method of diagnosing and treating cervical intraepithelial neoplasia (CIN).

First-line chemotherapy with epirubicin, paclitaxel, and carboplatin for advanced ovarian cancer: a phase I/II study of the Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group.

PURPOSE: Despite the progress that has been achieved over the years, survival rates in patients with advanced ovarian cancer are still disappointing. New methods to improve the efficiency of first-line chemotherapy are warranted. One method to improve results is to add more non-cross-resistant drugs to platinum-paclitaxel combination regimens. Anthracyclines are among the candidates for incorporation as the "third drug" into first-line regimens for advanced ovarian cancer. PATIENTS AND METHODS: We performed a phase I/II trial with escalating doses of epirubicin (60, 75, and 90 mg/m2) combined with fixed doses of paclitaxel and carboplatin in 27 previously untreated patients with advanced gynecologic malignancies. RESULTS: Dose-limiting toxicity occurred at dose level 2 (75 mg/m2 epirubicin) and consisted of myelosuppression (neutropenia, thrombocytopenia). No dose-limiting, nonhematologic toxicities were observed. The maximum tolerable dose was epirubicin 60 mg/m2 (E) combined with a 3-hour infusion of paclitaxel 175 mg/m2 (T) and carboplatin AUC 5 (Carbo). Preliminary analysis indicated promising activity against ovarian cancer. CONCLUSION: The three-drug combination ET-Carbo, given according to the outlined dose and schedule, should be considered for further phase III evaluation. A randomized German-French intergroup trial comparing ET-Carbo with carboplatin-paclitaxel has already been initiated.

[Screening for cervix carcinoma--a retrospective comparison between new and established federal German states]. / Screening auf Zervixkarzinom--ein rückblickender Vergleich zwischen den neuen und alten Bundesländern.

OBJECTIVE: There is no doubt about the effect of cytological screening programmes on the reduction of incident cases with invasive cervical carcinoma. The question is, to what extent this reduction was caused by cytological screening exclusively. A retrospective analysis of the former East German cytological mass screening could give information of early and late screening effects and also on the efficacy. Based on data from the Saarland cancer registry, common aspects and differences between the old and new federal states of Germany can be addressed regarding incidences and mortality trends for cervical carcinoma. RESULTS: Since the sixties the incidence of CIS has increased by 625% while the incidence of invasive carcinoma has decreased by 44% in the new federal states. Since the seventies mortality due to cervical carcinoma decreased by 44%. Incidences and mortality rates of the Saarland were considerably lower than of the new federal states. CONCLUSION: This study describes noteworthy early screening effects and proves the efficacy of mass cancer screening. Changes of incidence and, particularly, mortality rates are not exclusively due to these programmes.