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Spin-crossover (SCO) compounds are promising materials for a wide variety of industrial applications. However, the fundamental understanding of their nature of transition and its effect on the physical properties are still being fervently explored; the microscopic knowledge of their transition is essential for tailoring their properties. Here an attempt is made to correlate the changes in macroscopic physical properties with microscopic structural changes in the orthorhombic and monoclinic polymorphs of the SCO compound Fe(PM-Bia)2(NCS)2 (PM = N-2'-pyridylmethylene and Bia = 4-aminobiphenyl) by employing single-crystal X-ray diffraction, magnetization and DSC measurements. The dependence of macroscopic properties on cooperativity, highlighting the role of hydrogen bonding, π-π and van der Waals interactions is discussed. Values of entropy, enthalpy and cooperativity are calculated numerically based on the Slichter-Drickamer model. The particle size dependence of the magnetic properties is probed along with the thermal exchange and the kinetic behavior of the two polymorphs based on the dependence of magnetization on temperature scan rate and a theoretical model is proposed for the calculation of the non-equilibrium spin-phase fraction. Also a scan-rate-dependent two-step behavior observed for the orthorhombic polymorph, which is absent for the monoclinic polymorph, is reported. Moreover, it is found that the radiation dose from synchrotron radiation affects the spin-crossover process and shifts the transition region to lower temperatures, implying that the spin crossover can be tuned with radiation damage.
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As a consequence of demographic developments, legal questions regarding medical treatment of the elderly are receiving increasing attention. In the first instance, elderly patients are of course just normal patients. However, they often require a special degree of medical care from physicians and nurses. From a legal perspective, this leads to a heightened level of due diligence from medical practitioners. Specific legal challenges come into play when dealing with patients who are unable to give consent, or who are subject to personal custody. Additionally, patient's provisions and health care proxies are playing an ever more important role. Thus, an overview of the different legal aspects has become absolutely necessary for medical practitioners.
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Directivas Anticipadas , Geriatría , Anciano , Geriatría/ética , HumanosAsunto(s)
Procesamiento de Imagen Asistido por Computador/legislación & jurisprudencia , Informática Médica/legislación & jurisprudencia , Medicina Nuclear/legislación & jurisprudencia , Procesamiento de Imagen Asistido por Computador/normas , Difusión de la Información/legislación & jurisprudencia , Informática Médica/normas , Medicina Nuclear/normasRESUMEN
The lattice dynamics of Sb2Te3-x Se x (x = 0, 0.6, 1.2, 1.8, 3) mixed crystals have been studied by a combination of low-temperature heat-capacity measurements between 2-300 K and first-principles calculations. The results from the experimental and theoretical investigations are in excellent agreement. While Sb2Se3 can be considered as a harmonic lattice oscillator in this temperature range, for the isostructural compounds Sb2Te3, Sb2Se0.6Te2.4, Sb2Se1.2Te1.8 and Sb2Se1.8Te1.2 (tetradymite structure type; R [Formula: see text] m) a small anharmonic contribution to the total heat capacity has to be taken into account at temperatures above 250 K. For the compounds which crystallize in the tetradymite structure type the experimental and theoretical data show unambiguously that the exchange of Te by Se leads to an increase of the bonding polarity and consequently to a hardening of the bonding which is reflected in an increase of the Debye temperatures with increasing Se contents. In addition, our studies clearly demonstrate that the mixed crystals in the stability field of the tetradymite structure type are characterized by a strong non-ideal mixing behavior.
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BACKGROUND: HER2 is one of the predominant therapeutic targets in breast cancer. The metastatic selection process may lead to discrepancies between the HER2 status of the primary tumor and circulating tumor cells (CTCs). This study analyzed the HER2 status of CTCs in patients with HER2-positive primary breast cancer at the time of diagnosis. Aim of the study was to assess potential discordance of HER2 status between primary tumor and CTCs, as this may have important implications for the use of HER2-targeted therapy. METHODS: The number and HER2 status of CTCs out of 30ml peripheral blood were assessed in 642 patients using the CellSearch System (Janssen Diagnostics, USA). The cutoff for CTC positivity was the presence of at least 1 CTC, and the cutoff for HER2 positivity of CTCs was the presence of at least 1 CTC with a strong HER2 staining. RESULTS: 258 (40.2%) of the 642 patients were positive for CTCs (median 2; range 1-1,689). 149 (57.8%) of these 258 patients had at least 1 CTC with strong HER2 staining. The presence of HER2-positive CTCs was not associated with tumor size (p = 0.335), histopathological grading (p = 0.976), hormone receptor status (ER: p = 0.626, PR: p = 0.263) or axillary lymph node involvement (p = 0.430). Overall, 83 (32.2%) of the CTC-positive patients exclusively had CTCs with strong HER2 staining, whereas 31 (12.0%) had only CTCs with negative HER2 staining. Within-sample variation in the HER2 status of CTCs was found in 86 (57.8%) of the 149 patients with more than 1 CTC. CONCLUSION: This study demonstrated that discordance between the HER2 expression of CTCs and that of the primary tumor frequently occurs in early breast cancer. Future follow-up evaluation will assess whether this discrepancy may contribute to trastuzumab resistance.
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Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Células Neoplásicas Circulantes/patología , Receptor ErbB-2/genética , Adulto , Anciano , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Receptor ErbB-2/sangre , Investigación Biomédica Traslacional , Trastuzumab/administración & dosificaciónRESUMEN
Purpose: In order to achieve a higher vaccination rate, education on HPV as well as options for prophylaxis performed by doctors is of great importance. One opportunity to increase the protection against HPV would be vaccinating boys. This study evaluated attitude and knowledge among German gynecologists regarding HPV vaccination, especially in boys. Material and Methods: A questionnaire with 42 questions about demographics, attitude and knowledge about HPV and HPV vaccination was sent to members of the German Society for Gynecology and Obstetrics (DGGG). Results: 998 out of 6567 addressed gynecologists participated. Knowledge about HPV, associated diseases and possible HPV vaccines was high among participants. The attitude towards vaccination in boys as well as girls was positive. Only 8.2â% refused to vaccinate their sons whereas 2.2â% refused to do this for their daughters. However, only few gynecologists vaccinated their daughters and sons against HPV. Main reason for girls was an age outside of vaccination guidelines; for boys it was the lack of cost coverage. Conclusion: The willingness of gynecologists to perform HPV vaccination in boys is as high as for girls. However, sons of gynecologists are only rarely vaccinated against HPV. Main reason is the lack of cost coverage. Vaccinating boys could decrease the disease burden in males, as well as protect women by interrupting ways of transmission. Since the main argument against vaccination of boys is only of financial nature, the necessity of a vaccination recommendation for boys needs to be re-evaluated taking into account the cost-reduced 2-dose vaccination scheme.
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The crystal structure of ß-Na0.33V2O5 (C2/m, Z = 6) has been studied on compression to 19 GPa at room temperature using synchrotron single-crystal diffraction in a diamond anvil cell. The vanadate bronze undergoes a phase transition to a non-superconducting phase at about 12 GPa due to changes of polyhedral connectivities in the vanadate framework and due to ordering of the Na(+) cations. This novel structure (Cm, Z = 6) is interpreted as an intermediate stage in the sequence of pressure-induced transformations in the ß-A0.33V2O5 bronzes (A: Li, Na) at room temperature. This study reveals the close relation between the loss of the two-leg ladder V-V system and non-superconducting state of the ß-A0.33V2O5 materials.
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Obese breast cancer patients have a higher risk of lymph node metastasis and a poorer prognosis compared to patients with normal weight. For obese women with node-positive breast cancer, an association between body weight and prognosis remains unclear. In this retrospective study, we analyzed patient data from the Phase-III ADEBAR trial, in which high-risk breast cancer patients (pT1-4, pN2-3, pM0) were randomized into a docetaxel-based versus epirubicin-based chemotherapy regimen. Patients were grouped according to their BMI value as underweight/normal weight (BMI < 25 kg/m(2); n = 543), overweight (BMI 25-29.9 kg/m(2); n = 482) or obese (BMI ≥ 30 kg/m(2); n = 285). Overweight and obese patients were older, had larger tumors and were more likely to be postmenopausal at the time of diagnosis compared to underweight/normal-weight patients (all p < 0.001). Multivariate Cox regression analyses adjusting for age and histopathological tumor features showed that obese patients had a significantly shorter disease-free survival (DFS; HR 1.43; 95 % CI 1.11-1.86; p = 0.006) and overall survival (OS; HR 1.56; 95 % CI 1.14-2.14; p = 0.006) than non-obese patients. Subgroup analyses revealed that the differences in DFS and OS were significant for postmenopausal but not for premenopausal patients, and that the survival benefit of non-obese patients was more pronounced in women with hormone-receptor-positive disease. Obesity constitutes an independent, adverse prognostic factor in high-risk node-positive breast cancer patients, in particular for postmenopausal women and women with hormone-receptor-positive disease.
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Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/mortalidad , Obesidad/complicaciones , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor , Índice de Masa Corporal , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Ensayos Clínicos Fase III como Asunto , Femenino , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Estadificación de Neoplasias , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The oestrogenised vagina is colonised by Candida species in at least 20% of women; in late pregnancy and in immunosuppressed patients, this increases to at least 30%. In most cases, Candida albicans is involved. Host factors, particularly local defence mechanisms, gene polymorphisms, allergies, serum glucose levels, antibiotics, psycho-social stress and oestrogens influence the risk of candidal vulvovaginitis. Non-albicans species, particularly Candida glabrata, and in rare cases also Saccharomyces cerevisiae, cause less than 10% of all cases of vulvovaginitis with some regional variation; these are generally associated with milder signs and symptoms than normally seen with a C. albicans-associated vaginitis. Typical symptoms include premenstrual itching, burning, redness and odourless discharge. Although itching and redness of the introitus and vagina are typical symptoms, only 35-40% of women reporting genital itching in fact suffer from vulvovaginal candidosis. Medical history, clinical examination and microscopic examination of vaginal content using 400× optical magnification, or preferably phase contrast microscopy, are essential for diagnosis. In clinically and microscopically unclear cases and in chronically recurring cases, a fungal culture for pathogen determination should be performed. In the event of non-C. albicans species, the minimum inhibitory concentration (MIC) should also be determined. Chronic mucocutaneous candidosis, a rarer disorder which can occur in both sexes, has other causes and requires different diagnostic and treatment measures. Treatment with all antimycotic agents on the market (polyenes such as nystatin; imidazoles such as clotrimazole; and many others including ciclopirox olamine) is easy to administer in acute cases and is successful in more than 80% of cases. All vaginal preparations of polyenes, imidazoles and ciclopirox olamine and oral triazoles (fluconazole, itraconazole) are equally effective (Table ); however, oral triazoles should not be administered during pregnancy according to the manufacturers. C. glabrata is not sufficiently sensitive to the usual dosages of antimycotic agents approved for gynaecological use. In other countries, vaginal suppositories of boric acid (600 mg, 1-2 times daily for 14 days) or flucytosine are recommended. Boric acid treatment is not allowed in Germany and flucytosine is not available. Eight hundred-milligram oral fluconazole per day for 2-3 weeks is therefore recommended in Germany. Due to the clinical persistence of C. glabrata despite treatment with high-dose fluconazole, oral posaconazole and, more recently, echinocandins such as micafungin are under discussion; echinocandins are very expensive, are not approved for this indication and are not supported by clinical evidence of their efficacy. In cases of vulvovaginal candidosis, resistance to C. albicans does not play a significant role in the use of polyenes or azoles. Candida krusei is resistant to the triazoles, fluconazole and itraconazole. For this reason, local imidazole, ciclopirox olamine or nystatin should be used. There are no studies to support this recommendation, however. Side effects, toxicity, embryotoxicity and allergies are not clinically significant. Vaginal treatment with clotrimazole in the first trimester of a pregnancy reduces the rate of premature births. Although it is not necessary to treat a vaginal colonisation of Candida in healthy women, vaginal administration of antimycotics is often recommended in the third trimester of pregnancy in Germany to reduce the rate of oral thrush and napkin dermatitis in healthy full-term newborns. Chronic recurrent vulvovaginal candidosis continues to be treated in intervals using suppressive therapy as long as immunological treatments are not available. The relapse rate associated with weekly or monthly oral fluconazole treatment over 6 months is approximately 50% after the conclusion of suppressive therapy according to current studies. Good results have been achieved with a fluconazole regimen using an initial 200 mg fluconazole per day on 3 days in the first week and a dosage-reduced maintenance therapy with 200 mg once a month for 1 year when the patient is free of symptoms and fungal infection (Table ). Future studies should include Candida autovaccination, antibodies to Candida virulence factors and other immunological experiments. Probiotics with appropriate lactobacillus strains should also be examined in future studies on the basis of encouraging initial results. Because of the high rate of false indications, OTC treatment (self-treatment by the patient) should be discouraged.
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Antifúngicos/administración & dosificación , Candida albicans/efectos de los fármacos , Candidiasis Vulvovaginal/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/diagnóstico , Antifúngicos/uso terapéutico , Candida glabrata/efectos de los fármacos , Candidiasis Vulvovaginal/diagnóstico , Candidiasis Vulvovaginal/microbiología , Femenino , Alemania , Humanos , Recién Nacido , Pruebas de Sensibilidad Microbiana , Microscopía de Contraste de Fase , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/microbiología , Excreción VaginalRESUMEN
PURPOSE: A new CE-marked portable desktop ion mobility spectrometer (VGTest) was used for detection of malodorous biogenic amines indicative of bacterial vaginosis (BV). This study aimed to assess the performance of this testing method for the first time in a routine ambulatory care clinic and to determine the relative levels of biogenic amines in vaginal fluid of BV. METHODS: Vaginal and cervical swabs (n = 57) were surveyed for infections. Cases of BV (n = 18) confirmed positive according to "Amsel" criteria and normal controls (n = 39) showing no infection under clinical examination and testing negative in wet mount microscopy were included in the IMS analysis. RESULTS: The trimethylamine (TMA) content in vaginal fluid of the BV-positive cases, AUCTMA/AUCTotal [mean 0.215 (range 0.15-0.35)] was significantly higher than normal controls [mean 0.06 (range 0.048-0.07)] p < 0.0001. The putrescine (1,4-diaminobutane, PUT) and cadaverine (1,5-diaminopentane, CAD) of BV-positive cases were above controls at borderline significance. The AUCTMA/AUCTotal ratios correlated neither with AUCPUT/AUCTotal nor AUCCAD/AUCTotal among BV-positive patients. In contrast, among normal controls all the biogenic amines were at a low level and the linear regression analysis revealed striking positive correlations of AUCTMA/AUCTotal with AUCPUT/AUCTotal (p < 0.05) and AUCCAD/AUCTotal (p < 0.001). The test shows 83 % sensitivity and 92 % specificity at a cut-off of AUCTMA/AUCTotal = 0.112 and AUC of receiver operator characteristic = 0.915 (0.81-0.97, 95 % CI). CONCLUSIONS: VGTest-IMS is accurate and feasible for point-of-care testing of BV in the ambulatory care setting. Further evaluations are in progress to assess the utility of VGTest-IMS for differential diagnosis of candidosis, non-BV infection and common inflammatory conditions.
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Análisis Espectral/métodos , Vaginosis Bacteriana/diagnóstico , Adulto , Atención Ambulatoria/métodos , Líquidos Corporales , Cadaverina/análisis , Femenino , Humanos , Metilaminas/análisis , Persona de Mediana Edad , Sistemas de Atención de Punto , Putrescina/análisis , Sensibilidad y Especificidad , Vaginosis Bacteriana/microbiologíaRESUMEN
The lattice dynamics of polycrystalline Mg(2)Ge and Mg(2)Si are compared using both microscopic and macroscopic measurements as well as theoretical calculations. The volume thermal expansion coefficient between 200 and 300 K was found to be 4.37(5) · 10(-5) K(-1) in Mg(2)Ge, compared to 3.69(5) · 10(-5) K(-1) in Mg(2)Si. Inelastic neutron scattering measurements yield densities of phonon states which are in line with theoretical calculations. The microscopic data were corroborated with macroscopic calorimetry measurements and provide quantified values for anharmonicity. The estimated macroscopic Grüneisen parameter is, γ(Mg(2)Si) = 1.17(5) and γ(Mg(2)Ge) = 1.46(5) at 295 K, in excellent agreement with Raman scattering data. Although the element specific mean force constants are practically the same, in Mg(2)Ge and Mg(2)Si, a mass homology relation alone cannot reproduce the difference in the partial densities of vibrational states in these compounds and differences in elemental bonding should be taken into account.
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BACKGROUND: Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare. MATERIAL AND METHODS: We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC. RESULTS: The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P = 0.749), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P < 0.001). CONCLUSION: Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.
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Neoplasias de la Mama/patología , Recuento de Células/métodos , Citodiagnóstico/métodos , Inmunohistoquímica/métodos , Separación Inmunomagnética/métodos , Células Neoplásicas Circulantes/patología , Adulto , Anciano , Femenino , Alemania , Humanos , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Disseminated tumour cells (DTCs) in the bone marrow derive from many primary tumours, such as breast cancer. Their mere existence hints to present or future metastasis and implicates a worse prognosis for the patient. DTCs may possess different characteristics in comparison to the primary tumour due to events like Epithelial-Mesenchymal-Transition. Therefore, these cells might be able to survive chemotherapy and cause relapses of the disease at a later point. We aimed to detect and further characterise DTCs by an immunostaining approach with three different antigen markers (Her-2, MUC-1 and TF, also known as CD 176). For that reason, bone marrow of 41 breast cancer patients was obtained during surgery; DTCs were enriched by density gradient centrifugation and cytospins were prepared. After fixation, immunofluorescent double-stainings were carried out with antibodies against CD176 in combination with HER-2 or MUC-1. Cells co-expressing two antigens were found in all staining combinations (Her-2 and CD176: 46.14%; MUC-1 and CD176: 18.15% of all cases). Cells that stained for a single antigen only were also found (Her-2: 36.86%; MUC-1: 34.45%; CD176: 29.65% of all cases). Significant correlations between the stainings of all markers could be shown (p<0,001). In conclusion, Thomsen-Friedenreich Antigen (TF, CD176) is a promising marker in combination with the established marker Her-2 and other markers like MUC-1. These results may serve as a basis for future DTC detection routines and help to individualize medical treatment, reducing side effects and increasing the efficiency of the therapy.
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Biomarcadores de Tumor/análisis , Neoplasias de la Médula Ósea/diagnóstico , Neoplasias de la Mama/patología , Antígenos de Carbohidratos Asociados a Tumores/análisis , Antígenos de Carbohidratos Asociados a Tumores/biosíntesis , Neoplasias de la Médula Ósea/secundario , Femenino , Humanos , Inmunohistoquímica , Mucina-1/análisis , Mucina-1/biosíntesis , Receptor ErbB-2/análisis , Receptor ErbB-2/biosíntesisRESUMEN
The SUCCESS-A trial is a prospective, multicenter, phase III clinical trial for high-risk primary breast cancer. It compares disease-free survival after randomization in patients treated with fluorouracil, epirubicin and cyclophosphamide followed by 3 cycles of docetaxel (FEC-D) with that of patients treated with 3 cycles of FEC followed by 3 cycles of gemcitabine and docetaxel (FEC-DG). After a second randomization patients were treated with zoledronate for 2 or 5 years. A total of 251 centers took part in the trial and 3754 patients were recruited over a period of 18 months which ended in March 2007. In a questionnaire-based survey we investigated the impact of enrollment in the trial on patient care, the choice of chemotherapy protocol and access to current oncologic information as well as overall satisfaction in the respective centers. Analysis of the 78 questionnaires returned showed that 40â% of the centers had never previously enrolled patients with these indications in clinical studies. Prior to participating in the study, 4â% of the centers prescribed CMF or other protocols in patients with high-primary breast cancer risk, 46â% administered anthracycline-based chemotherapy and 50â% gave taxane-based chemotherapy. Around half of the participating centers noted that intensity of care and overall quality of care became even better and that access to breast cancer-specific information improved through participation in the trial. After their experience with the SUCCESS-A trial, all of the centers stated that they were prepared to enroll patients in clinical phase III trials again in the future. These data indicate that both patients and physicians benefit from clinical trials, as enrollment improves treatment strategies and individual patient care, irrespective of study endpoints.
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Introduction: The German DRG system is annually adapted to the changing services provided. For the further development, the self-governing body and its DRG Institute (InEK) depend on participation of the users. Methods: For one of the DRG evaluation projects initiated by DGGG, cost and performance data for the year 2011 from 16 hospitals were available. After plausibility checks and corrections, analyses for service and cost homogeneity were performed. In cases of inadequate DRG-representation attributes were sought that would make an appropriate reimbursement possible. Conspicuities and potential solutions were checked for clinical plausibility. Results: 44 concrete modification proposals for further development of the G-DRG system were formulated and submitted in due time to the InEK. In addition, 3 modification proposals were addressed to the German Institute for Medical Documentation and Information (Deutsches Institut für Medizinische Dokumentation und Information, DIMDI) for further development of the diagnosis classification ICD-10-GM. For all modification proposals care was taken to minimise misdirected incentives and to reduce the potential for disputes with the cost bearers and their auditors services in settlements. Discussion: The publication of the G-DRG system 2014 shows which modification proposals have been realised. Essentially, an appropriate redistribution of the resources among the gynaecological and obstetrics departments is to be expected. The financial pressure that is caused by the generally inadequate financing of hospitals will not be reduced by a further development of the G-DRG system.