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Background: Many reports on glioblastoma multiforme discuss the prognostic impact of anatomical features such as cysts, necrotic changes, extent of edema or subependymal spread of tumor cells. In the present study, we examined different growth patterns and their possible relations to patient survival. Methods: To analyze whether anatomical characteristics are related to prognosis, we reviewed the prospectively collected pre- and postoperative MRIs of 83 patients in the 5-ALA study, provided by the 5-ALA Glioma Study Group. Following a standardized analytic work flow, the tumor volume and site, presence of necrosis or cysts, and perifocal edema were assessed preoperatively. In the same way, postoperative MRI and the MRI at first recurrence were analyzed. In addition, survival time of the patients was documented. Results: Median survival time of all 83 patients was 15.1 months (range 1.5 to 70.1, mean 18). The site or volume of glioblastoma, as well as the presence of intratumoral necrosis or cysts, did not exert a significant effect on survival time; 96.4 % of recurrences occurred within the former resection margin. Tumors with initial contact with the subependymal zone had multifocal or ventricular recurrences significantly more often. In patients with residual tumor on early postoperative MRI, the follow-up images displayed enlargement of the remnants in 91.9 % of these cases. Conclusions: A merely anatomical analysis of the glioblastoma growth pattern cannot reliably provide prognostic information. The occurrence of most recurrences next to the resection margin and the high percentage of growing residual tumors underline the importance of complete resections. [ABSTRACT FROM AUTHOR]

The precursor of testicular germ cell tumours ( GCTs), called testicular intra-epithelial neoplasia ( TIN/ CIS), is safely diagnosed immunohistologically. Testicular biopsy provides a valuable tool for early detection of GCTs in risk groups. Although this knowledge is undisputed, testicular biopsies are utilized poorly. The patterns of care regarding the use of biopsies remain unknown. Uncertainty exists about the prevalence and specific treatment of TIN/ CIS. We asked clinical urologists in Germany whether or not they employed contralateral biopsies in GCT patients. We evaluated the prevalence of contralateral TIN/ CIS in a retrospective analysis of 780 consecutive GCT patients. All had contralateral double biopsies. Discordance of TIN/ CIS findings among biopsy pairs as well as age, histology of the primary tumour and clinical stage was noted. Evaluation of data comprised descriptive statistical methods. To evaluate treatment options for TIN/ CIS, we performed a literature search. 52.1% of German urologists always perform the biopsy, 17% do it mostly, 27.3% in select cases, 3.5% never. Curiously, there was a geographic north-south gradient regarding biopsy use. Contralateral TIN/ CIS was found in 5%. The median ages of patients with TIN/ CIS and those without were 31.8 and 34.9 years respectively ( p = 0.02). The discordance rate among biopsy pairs was of 33%. Two-site biopsies provide a 17% gain in diagnostic sensitivity. Local radiotherapy with 20 Gy is the safest treatment of TIN/ CIS failing in 2%. Chemotherapy has significantly lower efficacy. Contralateral testicular biopsies in GCT patients are well accepted among German urologists. The prevalence of contralateral TIN/ CIS found in this series is in accordance with previous reports. Double biopsies should be the diagnostic standard because of their diagnostic superiority. Local radiotherapy with 20 Gy is the safest way of eradicating TIN/ CIS. Failures occur in only 2%, usually many years after irradiation. Cisplatin-based chemotherapy is dose dependent and less effective. [ABSTRACT FROM AUTHOR]

Background: Contralateral testicular biopsy is a tool for early diagnosis of contralateral tumors in patients with testicular germ cell tumor (GCT). Though based on a high level of evidence, international guidelines do not unanimously recommend biopsies. We enquired the acceptance of contralateral biopsies among clinical urologists in Germany.Methods: A total of 326 urologic departments were asked by a questionnaire whether they perform contralateral biopsy in all cases with GCT, in most, in select cases, or never. In addition we enquired for type and size of the department as well as the annual volume of GCT patients. To specify the hospital geographically, we noted the ZIP code. The data were analyzed with descriptive statistical methods.Results: The response rate was 86.5%. Of the departments, 52.1, 17, 27.3, and 3.5% do the biopsy in all cases, in most of them, in select patients, and never, respectively. University departments have significantly lower acceptance of the procedure than general hospitals (50% versus 72.6%), even after adjusting for other hospital characteristics by multivariate analysis. There was no association of acceptance rate with hospital size and annual GCT volume. The biopsy is highly used in the northern parts of Germany and considerably under-used in southern regions.Conclusion: Contralateral testicular biopsy is well-established and widely accepted among clinical urologists in Germany. In other countries, biopsies remain controversial. Only in Denmark is it routinely employed. In Sweden, Austria, and Switzerland biopsies are done in selected patients. In view of the multination treatment consensus of GCT, explanations for the dissimilar biopsy rates in various countries remain elusive. Peculiar findings are the inferior acceptance rates in university departments and the north-south gradient within Germany. [ABSTRACT FROM AUTHOR]

Copyright of Der Urologe A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An alternative reduced-toxicity conditioning regimen for allogeneic transplantation, based on treosulfan and fludarabine, has recently been identified. The safety and efficacy of this new conditioning regimen has been investigated prospectively in patients with AML. A total number of 75 patients with AML in CR were treated with 3 × 14 g/m2 treosulfan and 5 × 30 mg/m2 fludarabine, followed by matched sibling or unrelated SCT. Patients were evaluated for engraftment, adverse events, GVHD, and for non-relapse mortality, relapse incidence, overall and disease-free survival (DFS). All patients showed primary engraftment of neutrophils after a median of 20 days. Non-hematological adverse events grade III-IV in severity included mainly infections (59%) and gastrointestinal symptoms (7%). Acute GVHD grade II-IV occurred in 21% and extensive chronic GVHD occurred in 16% of the patients. After a median follow-up of 715 days, the 2-year overall and DFS estimates were 61% and 55%, respectively. The 2-year incidences of relapse and non-relapse mortality reached 34% and 11%, respectively. In summary, our data confirm promising safety and efficacy of the treosulfan-based conditioning therapy in AML patients, ClinicalTrials.gov Identifier: NCT01063660. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDSs) often occur in older adults with significant comorbidities. Therefore, a reduced-toxicity conditioning regimen may be more suitable than standard conditioning regimens before allogeneic blood stem cell transplantation. Here, we retrospectively compare the outcome of a treosulfan-based conditioning regimen with standard myeloablative TBI-based conditioning regimens in patients (pts) with MDS. A total of 48 pts with MDS were included in the study, of which 29 (60%) pts received TBI-based and 19 (40%) pts received a treosulfan-based conditioning regimen. A significantly lower relapse incidence (5% vs 34% at 3 years, P=0.019) resulting in a better, but not statistically significant relapse-free survival (RFS) (57% vs 31%, P=0.086) was observed after treosulfan-based conditioning. In pts with increased risk for significant side effects due to comorbidities (haematopoietic stem cell transplantation specific comorbidity index), the estimated 3-year RFS was significantly better in the treosulfan group: 54% (95% confidence interval (CI), 17-90%) compared with pts in the TBI group: 11% (95% CI, 0-44%; log-rank test P=0.0455). Treosulfan-based conditioning therapy is a feasible and effective regimen for pts with MDS, especially in pts with preexisting comorbidities. [ABSTRACT FROM AUTHOR]

The pathogenesis of testicular germ cell tumours (GCTs) is potentially influenced by high-energy nutrition during infancy. As adult height is a proxy for childhood nutrition, we investigated the role of nutrition in GCT pathogenesis by comparing stature of patients with healthy men. In a matched case–control study, 6415 patients with GCT were compared with healthy army conscripts (1:6 matching modus) with regard to height (cm) and body mass index (BMI; kg/m2). Statistical analysis involved tabulation of descriptive height measures and BMI. Conditional logistic regression models were used to quantify the association of GCT with height, with odds ratios (OR) adjusted for BMI. The literature was searched for studies on stature in GCT patients. Body size is significantly associated with risk of GCT, very tall men (>195 cm) having a GCT risk of OR=3.35 (95% confidence intervals (CI): 2.88–3.90; adjusted). Short stature is protective (OR=0.798; 95% CI: 0.68–0.93). Both histologic subgroups are associated with tallness. Of 16 previous reports, 7 were confirmative, 5 had null and 4 equivocal results. The association of stature with GCT risk accords with the nutrition hypothesis of GCT. This study expands the current view of GCT tumorigenesis by suggesting that high-calorie intake in childhood promotes GCT precursors originating in utero.British Journal of Cancer (2008) 99, 1517–1521. doi:10.1038/sj.bjc.6604695 www.bjcancer.com Published online 30 September 2008 [ABSTRACT FROM AUTHOR]

Background: Adjuvant instillation therapy with chemo- or immunotherapeutic agents is an integral component in the treatment of non-muscle-invasive bladder cancer. There is, however, no general consensus on the choice of medication and the optimal duration of therapy. This multicenter trial compared a long-term treatment regimen with mitomycin C (MMC) with two short-term treatment approaches with MMC or bacille Calmette-Guérin (BCG) for intermediate-/high-risk bladder tumor after transurethral resection. In patients with low-risk bladder tumors, the effectiveness of six weekly MMC instillations was determined and compared with the results of patients not receiving adjuvant treatment.Material and Methods: A total of 495 patients with intermediate-/high-risk bladder tumor (recurrent and/or multifocal pTaG1, pTaG2-3, or pT1G1-3) were randomly administered either BCG-RIVM 2x108 CFU in six weekly instillations, MMC 20 mg in six weekly instillations, or MMC 20 mg in six weekly instillations with subsequent monthly instillations for 3 years. A total of 132 low-risk patients (first diagnosis of a unifocal pTaG1 bladder tumor) were randomly allocated to two treatment arms. In the first arm, 20 mg MMC were instilled weekly six times. In the control arm, the patients received no adjuvant therapy.Results: The 3-year recurrence-free rate in the patients of the intermediate-/high-risk group was 65.5% (95% CI: 55.9-73.5%) in the BCG arm and 68.6% (95% CI: 59.9-75.7%) in the MMC short-term arm. In the MMC long-term arm, the 3-year recurrence-free rate was significantly higher at 86.1% (95% CI: 77.9-91.4%, log-rank test: p=0.001). There was no increased toxicity observed with long-term administration of MMC. In the low-risk group, the 3-year recurrence-free rate after adjuvant therapy was 74% (95% CI: 60.0-83.8%) and in the patients receiving no adjuvant treatment 63% (95% CI: 46.6-75.5%, corresponding to a hazard ratio of 0.58 (95% CI: 0.28-1.18%). The difference between the treatment arms was not significant.Conclusion: Long-term prophylaxis with MMC results in a significantly reduced recurrence rate in intermediate-/high-risk bladder cancer with a comparable toxicity profile in comparison to short-term MMC or short-term BCG. Our study showed no significant decrease of the recurrence rate in low-risk tumors with six adjuvant MMC instillations. This treatment approach thus does not represent an alternative to early instillation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the efficacy and safety of subcutaneous (SC) versus oral administration of methotrexate (MTX) in patients with active rheumatoid arthritis (RA). METHODS: MTX-naive patients with active RA (Disease Activity Score in 28 joints >/=4) were eligible for the study if they had not previously taken biologic agents and had not taken disease-modifying antirheumatic drugs for 2 weeks prior to randomization. Patients were randomly assigned to receive 15 mg/week of MTX either orally (2 7.5-mg tablets plus a dummy prefilled syringe; n = 187 patients) or SC (prefilled syringe containing 10 mg/ml plus 2 dummy tablets; n = 188 patients) for 24 weeks. At week 16, patients who did not meet the American College of Rheumatology criteria for 20% improvement (ACR20) were switched from 15 mg of oral MTX to 15 mg of SC MTX and from 15 mg of SC MTX to 20 mg of SC MTX for the remaining 8 weeks, still in a blinded manner. The primary outcome was an ACR20 response at 24 weeks. RESULTS: At week 24, significantly more patients treated with SC MTX than with oral MTX showed ACR20 (78% versus 70%) and ACR70 (41% versus 33%) responses. Patients with a disease duration >/=12 months had even higher ACR20 response rates (89% for SC administration and 63% for oral). In 52 of the ACR20 nonresponders (14%), treatment was switched at week 16. Changing from oral to SC MTX and from 15 mg to 20 mg of SC MTX resulted in 30% and 23% ACR20 response rates, respectively, in these patients. MTX was well tolerated. The rate of adverse events was similar in all groups. CONCLUSION: This 6-month prospective, randomized, controlled trial is the first to examine oral versus SC administration of MTX. We found that SC administration was significantly more effective than oral administration of the same MTX dosage. There was no difference in tolerability. [ABSTRACT FROM AUTHOR]

The article presents a study which compared the efficacy and safety of subcutaneous (SC) versus oral administration of methotrexate (MTX) in patients with active rheumatoid arthritis (RA). The study found that at week 24, significantly more patients treated with SC MTX than with oral MTX showed ACR20 responses. It was also concluded that SC administration was significantly more effective than oral administration of the same MTX dosage.

To study the safety and efficacy of treosulfan, a cytotoxic alkylating agent, in patients with active secondary progressive multiple sclerosis. Treosulfan (L-threitol-1,4-bis(methanesulfonate)) is a bifunctional alkylating agent with a favorable profile of side effects, approved for the treatment of ovarian cancer. Treosulfan has previously been shown to reduce the severity of experimental allergic encephalomyelitis under pre-therapeutic and therapeutic conditions. In human peripheral blood mononuclear cells, treosulfan reduces proliferative capacity and increases apoptosis. This is a nonrandomized, open label study conducted in two centers. Eleven patients with active secondary progressive MS that failed to or did not qualify for approved disease modifying drugs were treated with treosulfan for 1 year. Patients received intravenous infusions of 7 g/m2 every 4 weeks for 3 months (cycles 1–4, induction phase) with a predefined one-step dose escalation, thereafter every 3 months for the following 9 months (cyles 5–7, maintainance phase). Cranial MRI was performed every 3 months, EDSS and MSFC as well as physical examination were assessed at each clinical visit. Treatment with treosulfan was safe and well tolerated. Nine of 11 patients remained on study drug over the complete treatment period and showed clinical stabilisation or improvement as determined by EDSS and MSFC. Two patients discontinued study drug because of leukocytopenia and withdrawal of consent, respectively. No clinical relapses were observed during the treatment period. Thus, the median number of relapses per year was reduced signifi- cantly by 1.5 (range –3 to 0), p < 0.016, compared to prestudy. Therapy with treosulfan lead to a clear reduction of MRI activity as revealed by a reduced number of Gd + enhancing lesions on T1 weighted images. The mean number and volume of T2 lesions remained unchanged over 1 year. Four out of 9 patients under treosulfan showed no detectable disease activity (no Gd enhancing lesions, no new or newly enlarging T2 lesions). Application of treosulfan in MS was safe and well tolerated. Further studies are warranted to evaluate the efficacy of this treatment in secondary progressive MS. [ABSTRACT FROM AUTHOR]

Background: The potential of autofluorescence bronchoscopy (AFB) to detect precancerous lesions in the central airways and its role in lung cancer screening is uncertain. A study was undertaken to evaluate the prevalence of moderate/severe dysplasia (dysplasia Il-Ill) and carcinoma in situ (CIS) using a newly developed AFB system in comparison with conventional white light bronchoscopy (WLB) alone. Methods: In a prospective randomised multicentre trial, smokers ⩾40 years of age (⩾20 pack-years) were stratified into four different risk groups and investigated with either WLB+AFB (arm A) or WIB alone (arm B). Results: 1173 patients (916 men) of mean age 58.7 years were included. Overall (arms A and B), preinvasive lesions (dysplasia Il-Ill and CIS) were detected in 3.9% of the patients. The prevalence of patients with preinvasive lesions in the WLB arm was 2.7% compared with 5.1% in the WLB+AFB arm (p = 0.037). For patients with dysplasia Il-Ill, WLB+AFB increased the detection rate by a factor of 2.1 (p = 0.03), while for CIS the factor was only 1.24 (p = 0.75). The biopsy based sensitivity of WLB alone and WIB+AFB for detecting dysplasia II-III and CIS was 57.9% compared with 82.3% (1.42-fold increase). The corresponding specificity was 62.1 % compared with 58.4% (0.94-fold decrease). Conclusions: This first randomised study of MB showed that the combination of WLB+AFB was significantly superior to WIB alone in detecting preneoplastic lesions. Our findings do not support the general use of AFB as a screening tool for lung cancer, but suggest that it may be of use in certain groups. The precise indications await further study. [ABSTRACT FROM AUTHOR]

Summary:Treosulphan has recently demonstrated antileukaemic activity and potent haematopoietic stem cell toxicity. Dose-escalated treosulphan (3×12 or 3×14?g/m2) combined with cyclophosphamide (Cy) was chosen for a new preparative regimen before allogeneic haematopoietic stem cell transplantation in 18 patients (median age 44, range 19-64 years) with haematological malignancies, considered ineligible for other myeloablative preparative regimens. Pharmacokinetic studies demonstrated rapid treosulphan plasma clearance and a dose-dependent increase of its maximum plasma concentrations and area under the concentration-time curves. Rapid and sustained white blood cell and platelet recovery and full donor chimerism was attained in all evaluable patients. Nonhaematological regimen-related CTC grades 3-4 adverse events were transient and predominantly consisted of cardiac (28%), gastrointestinal (39%), and hepatic (39%) toxicities. The 1-year nonrelapse mortality was 22%. Principal causes of transplant-related lethal events were infections in three of four affected patients. Only one patient died from regimen-related cardiac toxicity. The 1-year relapse estimate is 22%, overall and progression-free survival estimates are 67 and 56%, respectively. In conclusion, this new treosulphan and Cy combination is an effective, comparatively well-tolerated myeloablative preparative regimen even in patients with an increased risk for regimen-related toxic complications.Bone Marrow Transplantation (2005) 35, 233-241. doi:10.1038/sj.bmt.1704784 Published online 13 December 2004 [ABSTRACT FROM AUTHOR]

Clinical epidemiology is sometimes called the basic science of clinical medicine. In terms of the pathogenesis of testicular germ cell tumors (GCTs), clinical epidemiology analyzes suspected risk factors. The present review highlights the risk factors established so far and briefly summarizes those factors currently under investigation. In analogy to the methods of evidence based medicine, this review attributes levels of evidence to each of the putative risk factors. Level I represents highest quality of evidence while level V denotes the lowest level. So far, undescended testis (UDT), contralateral testicular GCT and familial testis cancer are established risk factors attaining high levels of evidence (levels I–III a). In a meta-analysis of 21 studies exploring the association of UDT with GCT risk, an over-all relative risk (RR) of 4.8 (95% confidence interval 4.0–5.7) was found. Contralateral testicular GCT involves a roughly 25-fold increased RR of GCT, while familial testis cancer constitutes a RR of 3–10. Infertility, testicular atrophy, and twin-ship represent risk factors with lesser levels of evidence (level III a). There is also some evidence for HIV infection being a predisposing factor for GCT (level IV a). Scrotal trauma is probably not associated with GCT risk. The estrogen excess theory implies high estrogen levels during the first trimester of pregnancy. As a consequence, primordial germ cells lose track of the normal developmental line and transform into premalignant cells that later become testicular intraepithelial neoplasia (TIN), the precursor of full-blown testicular GCT. Surrogate parameters for high gestational estrogen levels are investigated in case control studies. Such factors are maternal age >30 years, first-born, low birth weight, maternal breast cancer, high sex-ratio of siblings. So far, the sum of evidence is promising but still conflicting (especially for level III b). Another novel theory is the childhood nutrition hypothesis. This concept postulates a modulating or “catalyzing” effect by high dietary intake during childhood on the pathogenesis of testicular GCT. A surrogate parameter of early childhood nutrition is adult height. So far, 12 controlled studies have looked to the possible association of attained height and GCT risk of which six demonstrated a significant association. Thus, the sum of evidence corresponds to level III b. This concept is appealing because it would explain several hitherto unexplained epidemiological features of GCT. [ABSTRACT FROM AUTHOR]

A prospective monocentre randomized parallel-group Phase III trial was performed to investigate whether primary transurethral resection (TUR) with 5-aminolevulinic acid induced Fluorescence diagnosis (FD) allows for a more thorough TUR of superficial Bladder Carcinoma compared to conventional white light (WL). Evaluation of residual tumor rate and recurrence free survival were defined as the two primary study endpoints. The residual tumor rate was 25.2% in the WL arm (n=103) vs. 4.5% in the (n=88) FD arm (p<0.0001). Median follow up of the patients in the WL arm was 42 months (range 25-61) compared to 43 (range 24-61) in the FD arm. Recurrence free survival in the fluorescence diagnosis group was 90.9%, 90.9% und 85 % after 12, 24 and 48 months compared with 78.6%, 69.9% und 60.7 %, respectively, in the white light group (p=0.0005). This superiority proved to be independent of risk group. The adjusted hazard ratio of fluorescence diagnosis versus white light transurethral resection was 0.29 (95% CI: [0.15; 0.56]). ALA induced FD is statistically significantly superior to conventional WL TUR with respect to both residual tumor rate and recurrence-free survival. The differences in RFS imply that FD offers a clinically relevant procedure to reduce the number of tumor recurrences. [ABSTRACT FROM AUTHOR]

Copyright of Der Onkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The relationship between interleukin-6 (IL-6) and the soluble interleukin-6 receptor (sIL-6R) was analyzed in 1481 serum samples of 82 patients after bone marrow or peripheral blood cell transplantation. The cytokine and its soluble receptor were measured on a daily basis starting at day -3 before and ending at day 21 after transplantation. IL-6 serum levels increased after transplantation, were at a maximum at day 6 and returned to the baseline level thereafter. The levels of sIL-6R showed an inverse course with a minimum at day 6. Statistical analysis revealed a strong inverse correlation between IL-6 and sIL-6R with a weighted Spearman rank correlation coefficient of -0.53 (P < 0.001). il-6 may play a role in the decrease of sil-6r either by the direct inhibitory effect on the expression of the il-6r gene or by formation of il-6/sil-6r complexes followed by their internalization in target cells. [ABSTRACT FROM AUTHOR]

Introduction: A prospective monocenter open study was carried out to evaluate if generalized phototoxic skin reactions occur after intravesical application of 5-aminolevulinic acid (ALA) for fluorescence diagnosis of superficial bladder carcinomas. Patients and Methods: On 21 patients, skin phototoxicity was determined prior to as well as 4, 8 and 28 h after intravesical instillation of a 3% ALA solution by exposing small skin areas to a progressively graded series of defined UVA-light doses (n = 9; 5–80 J/cm[sup 2] ). Results: Prior to ALA instillation, erythema or pigmentation as signs of cutaneous phototoxicity occurred at an UVA-light dose of 28 ± 1.5 J/cm[sup 2] (mean ± SEM). A reduction of the minimal phototoxic dose (MPD) was not detected 4 (28 ± 1.9 J/cm[sup 2] ), 8 (28 ± 1.6 J/cm[sup 2] ) and 28 h (28 ± 1.5 J/cm[sup 2] ) after ALA instillation. Consequently phototoxic reactions were not observed. Conclusions: A reduction of MPD for UVA was not detected. Therefore, it is not necessary to protect the skin of patients from ambient or daylight after intravesical instillation of ALA for fluorescence diagnosis.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article focuses on validated strategy to select patients for a Nerve-sparing radical prostatectomy (NSRP). Topics include NSRP for the treatment of prostate cancer (PCA) should be restricted to patients who harbor tumors without capsular penetration; and association of clinical stage, serum prostate specific antigen (PSA) results of transrectal ultrasonography (TRUS) anf systematic sextant biopsy that include highgrade cancer and number of biopsies.

Nerve-sparing radical prostatectomy (NSRP) for the treatment of prostate cancer (PCA) should be restricted to patients who harbour tumours without capsular penetration. Selection criteria for NSRP are not clearly defined. We investigated a panel of preoperative tumour characteristics with respect to their ability to predict organ-confined tumour growth for each lobe of the prostate to indicate uni- or bilateral NSRP. [ABSTRACT FROM AUTHOR]