Benign uterine mass-discrimination from leiomyosarcoma by a preoperative risk score: a multicenter cohort study.

PURPOSE: Discrimination of uterine leiomyosarcoma (LMS) and leiomyoma (LM) prior to surgery by basic preoperative characteristics and development of a preoperative leiomyosarcoma score. METHODS: A predominantly prospective cohort of 826 patients with LM from a clinical institution and an outpatient center was included in the study. Further a predominantly retrospective cohort of 293 patients with LMS was included from the counseling database of the German Clinical Center of Excellence for Genital Sarcoma and Mixed Tumors (DKSM, University Medicine Greifswald, Germany). We analyzed and compared anamnestic, epidemiological and clinical findings between both cohorts. Tenfold cross-validated logistic regression and random forest was performed on the 80% training set. The preoperative LMS score (pLMS) was developed based on logistic regression and independently evaluated by analyzing the area under the receiver operating characteristic curve (AUC) with the 20% test set. RESULTS: In the LMS cohort, 63.1% had initially surgery for presumed LM and only 39.6% of endometrial biopsies revealed LMS. Key features for LMS discrimination were found to be bleeding symptoms: intermenstrual bleeding [RRc = 2.71, CI = (1.90-3.49), p < 0.001], hypermenorrhea [RRc = 0.28, CI = (0.15-0.50), p < 0.001], dysmenorrhea [RRc = 0.22, CI = (0.10-0.51), p < 0.001], postmenstrual bleeding [RRc = 2.08, CI = (1.30-2.75), p < 0.001], suspicious sonography [RRc = 1.21, CI = (1.19-1.22), p < 0.001] and the tumor diameter (each centimeter difference: ß = 0.24, SD = 0.04, p < 0.001). pLMS achieved a mean cross-validated AUC of 0.969 (SD = 0.019) in the training set and an AUC of 0.968 in the test set. CONCLUSIONS: The presented score is based on basic clinical characteristics and allows the prediction of LMS prior to a planned surgery of a uterine mass. In case pLMS is between - 3 and + 1, we suggest subsequent diagnostics, such as endometrial biopsy, color Doppler sonography, LDH measurement, MRI and transcervical biopsy.

Clinical Outcome of Neoadjuvant Radiochemotherapy in Locally Advanced Cervical Cancer: Results of an Open Prospective, Multicenter Phase 2 Study of the North-Eastern German Society of Gynecological Oncology.

OBJECTIVE: The aim of this study was to determine the response rate, toxicity, operability, and surgical complication rate of neoadjuvant concomitant radiochemotherapy (cRCH) (ifosfamide + carboplatin) followed by radical hysterectomy plus external-beam radiotherapy with curative intention in locally advanced primary inoperable stages IIB and IIIB squamous cell cervical cancer. METHODS: Patients with cervical cancer from 8 departments were enrolled. Patients received 3 cycles of ifosfamide 1.2 mg/m (+mesna 20%) plus carboplatin (area under the curve = 4), every 21 days, and concomitant external-beam radiotherapy (50.4 Gy [1.8 Gy/d]). Operability and remission were evaluated by clinical gynecological examination in general anesthesia (magnetic resonance imaging was optional), 4 weeks after the third cycle of cRCH. In case of achieved operability, a radical hysterectomy with pelvic lymphadenectomy was performed within 6 weeks after cRCH. If surgery was not performed because of incomplete remission or patient preferences, vaginal brachytherapy (15 Gy [5 Gy/d]) was given additionally. RESULTS: Forty-four patients were enrolled. Distribution of FIGO (International Federation of Gynecology and Obstetrics) tumor stage was as follows: IIB (19 patients) and IIIB (25 patients). All patients completed cRCH. Grade 3/4 hematologic toxicities (% of all cycles) were moderate: leukopenia, 7.3; thrombocytopenia, 2.4; and anemia, 3.2. In 13.8%, treatment cycles were delayed because of hematologic toxicity. Blood transfusions were given in 17.7% and granulocyte colony-stimulating factor in 39.5%. Overall, grade 3/4 nonhematologic toxicities were seldom (6.5%). Clinical overall response rate was 95.2%. Operability was achieved in 85.7%. Surgery was performed in 83.3%. Pathological response rates were as follows: pathological complete remission, 33.3%; partial remission, 63.3%; stable disease, 3.3%. CONCLUSIONS: Our study demonstrates that cRCH is an effective and tolerable regimen in locally advanced cervical cancer treatment.

Accidental Morcellation of Uterine Leiomyosarcoma Influences Relapse Free Survival but Does Not Negatively Influence Overall Survival.

Background: Uterine leiomyosarcoma (LMS) is a rare entity amongst malignant gynaecological tumours and is mostly diagnosed after surgery for benign leiomyoma (LM) of the uterus. As minimal invasive surgery is widely used, the morcellation of LM and the uterus is rather common. As there is little known about the impact of the morcellation of LMS on local and distant metastases, as well as overall survival, we carried out a large-scale retrospective study. Methods: A total of 301 LMS cases from the German Clinical Competence Centre for Genital Sarcomas and Mixed Tumours were analysed. We distinguished morcellated and non-morcellated LMS from pT1 and >pT1 tumours. Fine−Gray competing risks regressions and cumulative incidence rates were computed for the time to local recurrence, distant metastases, and patient death. Results: The recurrence free interval in pT1 LMS was significantly lower in the morcellation group with a 2-year cumulative incidence rate of 49% vs. 26% in non-morcellated LMS (p = 0.001). No differences were seen in >pT1 tumours. Distant metastases were more frequently found in non-morcellated pT1 LMS compared to the morcellated cases (5-year cumulative incidence: 54% vs. 29%, p < 0.001). There was no significant difference in time to death between both groups neither in the pT1 stages nor in >pT1 disease. Subdistribution hazard ratios estimated by multivariable competing risks regressions for the morcellation of pT1 LMS were 2.11 for local recurrence (95% CI 1.41−3.16, p < 0.001) and 0.52 for distant metastases (95% CI 0.32−0.84, p = 0.008). Conclusions: Tumour morcellation is not associated with OS for pT1 tumours. The morcellation of pT1 LMS seems to prolong the time to distant metastases whereas local recurrence is more likely to occur after the morcellation of pT1 LMS.

Vulvar Leiomyosarcomas: A Case Series with Clinical Comparison to Uterine Leiomyosarcomas and Review of the Literature.

BACKGROUND Leiomyosarcomas of the vulva (VLMS) are very rare among gynecological malignancies, with a lack of knowledge on clinical presentation, prognosis, and therapeutic management. CASE REPORT The database of the German Clinical Center of Competence for Genital Sarcomas and Mixed Tumors in Greifswald (DKSM) was reviewed between the years 2010 and 2020. A total of 8 cases of VLMS were retrieved and analyzed retrospectively. One exemplary case of VLMS was outlined in detail: A 45-year-old premenopausal woman presented with increasing vulvar swelling and discomfort. Given the suspicion of a Bartholin's gland abscess, the mass was excised. Final pathology revealed a solid tumor consistent with a moderately differentiated leiomyosarcoma of the vulva. A wide local excision was subsequently performed followed by adjuvant external beam radiation. The clinical features of these 8 cases of VLMS were compared to 26 cases of VLMS found in a review of the literature and to a total of 276 cases of uterine leiomyosarcoma (ULMS) from the same database (DKSM). CONCLUSIONS In addition to rapid growth, observed in both tumor entities, VLMS most commonly presented as Bartholin's gland abscess or cyst and ULMS as leiomyoma. In this cohort, the prognosis of VLMS was much better than that of ULMS, most probably due to the significantly smaller tumor size of VLMS at diagnosis. Further data and larger studies on VLMS are needed to calculate recurrence and survival rates more accurately and define the role of adjuvant radiotherapy.

Sarcoma of the Uterus. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/074, April 2021).

Purpose This is an official guideline, published and coordinated by the Germany Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG). Because of their rarity and heterogeneous histopathology, uterine sarcomas are challenging in terms of their clinical management and therefore require a multidisciplinary approach. To our knowledge, there are currently no binding evidence-based recommendations for the appropriate management of this heterogeneous group of tumors. Methods This S2k guideline was first published in 2015. The update published here is once again the result of the consensus of a representative interdisciplinary committee of experts who were commissioned by the Guidelines Committee of the DGGG to carry out a systematic search of the literature on uterine sarcomas. Members of the participating professional societies achieved a formal consensus after a structured consensus process. Recommendations 1.1 Epidemiology, classification, staging of uterine sarcomas. 1.2 Symptoms, general diagnostic workup, general pathology or genetic predisposition to uterine sarcomas. 2. Management of leiomyosarcomas. 3. Management of low-grade endometrial stromal sarcomas. 4. Management of high-grade endometrial stromal sarcoma and undifferentiated uterine sarcomas. 5. Management of adenosarcomas. 6. Rhabdomyosarcomas of the uterus in children and adolescents. 7. Follow-up of uterine sarcomas. 8. Management of morcellated uterine sarcomas. 9. Information provided to patients.

Plant species richness in montane grasslands affects the fitness of a generalist grasshopper species.

Theory predicts negative effects of increasing plant diversity on the abundance of specialist insect herbivores, but little is known about how plant diversity affects the performance and abundance of generalist insect herbivores. We studied oviposition rates and offspring numbers in females of the generalist grasshopper Chorthippus parallelus that were collected in 15 montane grasslands in 2005 and 2007 along a gradient of plant species richness in central Germany. In addition to plant species richness, we determined evenness and plant community composition in the grasslands and measured aboveground plant biomass and other habitat variables such as leaf area index, vegetation height, and solar radiation. There was substantial variation among sites in grasshopper fecundity and the number of nymphs that hatched from the egg pods. Both fitness measures were positively influenced by plant species richness at the sites, while female fitness did not correlate with any of the other habitat parameters. Abundance of C. parallelus in the grasslands was positively correlated with plant species richness, plant community composition, and incident solar radiation of the sites. There were no phenological differences between grasshoppers from the different study sites. Our results suggest that decreasing biodiversity threatens the persistence not only of specialist, but also of generalist insect herbivores via a variety of mechanisms including a decrease in diversity of the generalists' food plants.

Functional identity versus species richness: herbivory resistance in plant communities.

The resistance of a plant community against herbivore attack may depend on plant species richness, with monocultures often much more severely affected than mixtures of plant species. Here, we used a plant-herbivore system to study the effects of selective herbivory on consumption resistance and recovery after herbivory in 81 experimental grassland plots. Communities were established from seed in 2002 and contained 1, 2, 4, 8, 16 or 60 plant species of 1, 2, 3 or 4 functional groups. In 2004, pairs of enclosure cages (1 m tall, 0.5 m diameter) were set up on all 81 plots. One randomly selected cage of each pair was stocked with 10 male and 10 female nymphs of the meadow grasshopper, Chorthippus parallelus. The grasshoppers fed for 2 months, and the vegetation was monitored over 1 year. Consumption resistance and recovery of vegetation were calculated as proportional changes in vegetation biomass. Overall, grasshopper herbivory averaged 6.8%. Herbivory resistance and recovery were influenced by plant functional group identity, but independent of plant species richness and number of functional groups. However, herbivory induced shifts in vegetation composition that depended on plant species richness. Grasshopper herbivory led to increases in herb cover at the expense of grasses. Herb cover increased more strongly in species-rich mixtures. We conclude that selective herbivory changes the functional composition of plant communities and that compositional changes due to selective herbivory depend on plant species richness.

Polypropylene mesh implantation in combination with vacuum-assisted closure in the management of metastatic or locally recurrent vulvar cancer: case report and review of literature.

BACKGROUND: Mesh reconstruction, especially in combination with vacuum-assisted closure, might improve healing and reduce the surgical morbidity of extensive inguinofemoral lymphadenectomy or extensive local resection in progressive cancer of the vulva. CASES: Radical vulvectomy combined with inguinofemoral lymphadenectomy was performed in 2 patients (P1, P2). The inguinofemoral wound bed was stabilized by polypropylene mesh implantation and sealed with vacuum closure system. In 1 patient with local recurrence of vulvar cancer (P3), local excision and stabilization of the wound were performed by mesh implantation. CONCLUSIONS: Mesh implantation fulfills 2 purposes: (1) it protects exposed vessels and the wound can be vacuum sealed; and (2) it stabilizes the surgical bed, permitting the required radical excision locally and inside the vascular compartment.

Green-brown polymorphism in alpine grasshoppers affects body temperature.

Ectothermic animals depend on external heat sources for pursuing their daily activities. However, reaching sufficiently high temperature can be limiting at high altitudes, where nights are cold and seasons short. We focus on the role of a green-brown color polymorphism in grasshoppers from alpine habitats. The green-brown polymorphism is phylogenetically and spatially widespread among Orthopterans and the eco-evolutionary processes that contribute to its maintenance have not yet been identified.We here test whether green and brown individuals heat up to different temperatures under field conditions. If they do, this would suggest that thermoregulatory capacity might contribute to the maintenance of the green-brown polymorphism.We recorded thorax temperatures of individuals sampled and measured under field conditions. Overall, thorax temperatures ranged 1.7-42.1°C. Heat up during morning hours was particularly rapid, and temperatures stabilized between 31 and 36°C during the warm parts of the day. Female body temperatures were significantly higher than body temperatures of males by an average of 2.4°C. We also found that brown morphs were warmer by 1.5°C on average, a pattern that was particularly supported in the polymorphic club-legged grasshopper Gomphocerus sibiricus and the meadow grasshopper Pseudochorthippus parallelus.The difference in body temperature between morphs might lead to fitness differences that can contribute to the maintenance of the color polymorphism in combination with other components, such as crypsis, that functionally trade-off with the ability to heat up. The data may be of more general relevance to the maintenance of a high prevalence polymorphism in Orthopteran insects.

Sarcoma of the Uterus. Guideline of the DGGG and OEGGG (S2k Level, AWMF Register Number 015/074, February 2019).

Aims This is an official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). Because of their rarity and heterogeneous histopathology, uterine sarcomas are challenging in terms of how they should be managed clinically, and treatment requires a multidisciplinary approach. To our knowledge, there are currently no binding evidence-based recommendations for the appropriate management of this heterogeneous group of tumors. Methods This S2k guideline was first published in 2015. The update published here is the result of the consensus of a representative interdisciplinary group of experts who carried out a systematic search of the literature on uterine sarcomas in the context of the guidelines program of the DGGG, OEGGG and SGGG. Members of the participating professional societies achieved a formal consensus after a moderated structured consensus process. Recommendations The consensus-based recommendations and statements include the epidemiology, classification, staging, symptoms, general diagnostic work-up and general pathology of uterine sarcomas as well as the genetic predisposition to develop uterine sarcomas. Also included are statements on the management of leiomyosarcomas, (low and high-grade) endometrial stromal sarcomas and undifferentiated uterine sarcomas and adenosarcomas. Finally, the guideline considers the follow-up and morcellation of uterine sarcomas and the information provided to patients.

Diversity and beyond: plant functional identity determines herbivore performance.

1. Recent biodiversity studies have addressed various community-level effects of biodiversity change, but the number of studies on specific biotic interactions is still rather limited. An open question in the context of plant-insect-herbivore relationships is how diversity impacts the population ecology of individual species. 2. In the present study, we explored the relationship between plant species diversity and the performance and fitness of a generalist herbivore, the meadow grasshopper Chorthippus parallelus Zetterstedt (Orthoptera, Gomphocerinae). A total of 1620 fourth-instar nymphs of this insect were captured and transferred to cages (10 females and 10 males per cage) on 81 experimental grassland communities in plots containing one to 60 plant species within the Jena biodiversity experiment. 3. Median survival of grasshoppers in the experiment was 14.5 days. Survival was independent of plant species richness and number of plant functional groups in the communities, but increased if plant communities contained grasses. Plant species richness and plant functional group richness had no effect on the number of oothecae laid by females or the number of hatchlings in the next generation. 4. Functional group composition of the plant communities affected most fitness measures. Grass presence increased the number of oothecae laid by females from 0.78 +/- 0.21 to 3.7 +/- 0.41 per female, and the number of hatchlings in the next generation from 4.0 +/- 1.3 to 16.6 +/- 2.4. Certain combinations of plant functional groups increased grasshopper survival. 5. The findings indicate that the fitness of C. parallelus is influenced more by plant functional group identity than by plant species richness. In the absence of grasses, grasshoppers performed better if more than just one functional group of plants was present. We call this a 'rescue effect' of plant functional group richness.

Staging procedures in primary breast cancer.

BACKGROUND: In consideration of increasing incidence by introduction of screening mammography, the prevalence of distant metastases and necessity of staging procedures in early breast cancer should be proved. PATIENTS AND METHODS: A retrospective review was undertaken of 466 patients with newly diagnosed breast cancer in the period from 2003 to 2006. RESULTS: Distant metastases were found in 22 (4.8%) patients at the time of primary diagnosis of breast cancer. None of these patients had a tumour < or =1 cm and the percentage of metastatic disease increased with local extension (pT1 1.4%; pT2 7.9%; pT3 14.3%; pT4 23.1%; p<0.001) and nodal status (pN0 1.7%; pN1 3.8%; pN2 21.7%; pN3 17.6%; p<0.001) CONCLUSION: Indication for bone scan, liver ultrasound and chest x-ray should be limited to patients with tumours >2 cm, or tumours >1 cm with lymph node involvement (N1-3).

Significance of laboratory studies for ruling out metastases in primary endometrial carcinoma.

BACKGROUND: At the time of initial diagnosis of endometrial cancer, therapeutic decisions depend on the recognition of remote metastases. Tumor markers and hepatic enzymes are frequently used to screen for metastases. This study aimed to assess the clinical value of serum concentrations of tumor markers and liver enzymes. PATIENTS AND METHODS: Laboratory test results from all patients with the initial diagnosis of endometrial cancer treated in our department between 1990 and 2000 were retrospectively reviewed. Hepatic enzyme levels and tumor markers relevant for endometrial cancer were recorded. Analysis of variance and post hoc tests were used to rule out or to confirm systematic differences. Significances were examined by the Mann-Whitney test. RESULTS: A total of 336 women were included in the analysis. Recorded data included serum concentrations of alanine aminotranspherase (ALT) (n = 228), aspartate aminotranspherase (AST) (n = 289), gamma-glutamyltranspherase (Gamma-GT) (n = 176) and alkaline phosphatase (AP) (n = 86). The following tumor markers were analysed: carcinoembryonic antigen (CEA) (n = 182), squamous cell carcinoma antigen (SCC) (n = 40), cancer-associated serum antigen (CASA) (n = 10), CA 15-3 (n = 5), CA 19-9 (n = 21), and CA 125 (n = 28). Only CEA serum levels differed significantly between patients with endometrial cancer and hepatic and pulmonary metastases at the time of initial diagnosis and patients without metastases. CONCLUSION: Our data show that neither the level of the tumor markers CEA, SCC, CA 15-3, CA 125, CA 19-9, CA 72-4 and CASA nor the hepatic enzymes AST, ALT, Gamma-GT and AP in routine evaluation accurately predict the presence of remote metastases.

Morphological and colour morph clines along an altitudinal gradient in the meadow grasshopper Pseudochorthippus parallelus.

Many animals show altitudinal clines in size, shape and body colour. Increases in body size and reduction in the length of body appendices in colder habitats are usually attributed to improved heat conservation at lower surface-to-volume ratios (known as Bergmann's and Allen's rule, respectively). However, the patterns are more variable and sometimes reversed in small ectotherms that are affected by shortened growing seasons. Altitude can also affect colouration. The thermal melanism hypothesis predicts darker colours under cooler conditions because of a thermoregulatory advantage. Darker colours may also be favoured at high altitudes for reasons of UV protection or habitat-dependent crypsis. We studied altitudinal variation in morphology and colour in the colour-polymorphic meadow grasshopper Pseudochorthippus parallelus based on 563 individuals from 17 populations sampled between 450 and 2,500 m asl. Pronotum length did not change with altitude, while postfemur length decreased significantly in both sexes. Tegmen (forewing) length decreased in males, but not in females. The results indicate that while body size, as best quantified by pronotum length, was remarkably constant, extended appendices were reduced at high altitudes. The pattern thus follows Allen's rule, but neither Bergmann's nor converse Bergmann's rule. These results indicate that inference of converse Bergmann's rule based on measurements from appendices should be treated with some caution. Colour morph ratios showed significant changes in both sexes from lowland populations dominated by green individuals to high-altitude populations dominated by brown ones. The increase of brown morphs was particularly steep between 1,500 and 2,000 m asl. The results suggest shared control of colour in males and females and local adaptation along the altitudinal gradient following the predictions of the thermal melanism hypothesis. Interestingly, both patterns, the reduction of body appendices and the higher frequency of brown individuals, may be explained by a need for efficient thermoregulation under high-altitude conditions.

[Multi-institutional survey on the value of lymphadenectomy in endometrial carcinoma in Germany]. / Multizentrische Umfrage zum Stellenwert der Lymphonodektomie beim Endometriumkarzinom in Deutschland.

INTRODUCTION AND OBJECTIVE: Primary surgical staging has been established in the management of carcinoma of the endometrium. Various working groups have also recommended the use of lymphadenectomy. Contrary to the prognostic relevance of lymph node status, the therapeutic value of lymphadenectomy is still unclear. METHOD: A total of 1,030 standardised questionnaires were sent to gynaecological clinics (including in-patient clinics) in Germany as part of a cross-sectional study between October 2001 and January 2002. RESULTS: It was possible to evaluate 595 (58%) of the questionnaires from 5.2% university clinics, 69.7% clinics for maximal treatment and 25% clinics for regular therapy. Is a lymphadenectomy performed in the case of a carcinoma of the endometrium? Only 7.3%(95% Cl: 5.3-9.7%) reported that they never performed a lymphadenectomy, 62.9% (95% Cl: 58.9-66.9%) performed one in special cases, 29.7 (95% Cl: 26-33.7%) did so regularly. Which methods do you use for lymphadenectomy? 27.1% (95% Cl: 23.2-31.4%) used'sampling' and 72.9% (95% Cl 68.6-76.8%) used the technique of systematic removal. 26.6% lymph node dissections were both pelvic as well as para-aortic. What is your intention when performing a lymphadenectomy? 31.7% (95 Cl: 22.8-30.6%) performed it for stag-ing reasons, 3.1% (95% Cl: 1.8-4.9%) for the patient's survival and 65.2% (95% Cl: 60.9-69.3%) for both of these reasons. 94.5% (95% Cl:92.1-96.3%) said that the status of the affected lymph nodes influenced the choice of adjuvant treatment. 76.8% (95% Cl: 72.8-80.4%) and 36.9% (95% Cl: 46.9-56.5%) chose radiotherapy in stages I/II and III/IV, respectively; 20.4% (95% Cl: 16.9-24.2%) and 51.7%(95% Cl: 46.9-56.5%) chose radiochemotherapy. CONCLUSIONS: The conception of prospective, multicentric studies of operative and adjuvant management should be based on these results.

Effects of habitat structure and land-use intensity on the genetic structure of the grasshopper species Chorthippus parallelus.

Land-use intensity (LUI) is assumed to impact the genetic structure of organisms. While effects of landscape structure on the genetics of local populations have frequently been analysed, potential effects of variation in LUI on the genetic diversity of local populations have mostly been neglected. In this study, we used six polymorphic microsatellites to analyse the genetic effects of variation in land use in the highly abundant grasshopper Chorthippus parallelus. We sampled a total of 610 individuals at 22 heterogeneous grassland sites in the Hainich-Dün region of Central Germany. For each of these grassland sites we assessed habitat size, LUI (combined index of mowing, grazing and fertilization), and the proportion of grassland adjoining the sampling site and the landscape heterogeneity (the latter two factors within a 500 m buffer zone surrounding each focal site). We found only marginal genetic differentiation among all local populations and no correlation between geographical and genetic distance. Habitat size, LUI and landscape characteristics had only weak effects on most of the parameters of genetic diversity of C. parallelus; only expected heterozygosity and the grasshopper abundances were affected by interacting effects of LUI, habitat size and landscape characteristics. The lack of any strong relationships between LUI, abundance and the genetic structure might be due to large local populations of the species in the landscape, counteracting local differentiation and potential genetic drift effects.

A fecundity cost of (walking) mobility in an insect.

Evolutionary theory predicts trade-offs between fecundity and mobility, but there is substantial lack of empirical evidence if and how basic mobility relates to fitness costs. In a field experiment, we investigated fecundity costs of mobility in a non-migratory, wing-monomorphic grasshopper, Stenobothrus lineatus, and at the same time tested for possible effects of reproductive state (egg-load) on the mobility. For 10 days, body weight and activity radius of 60 females were recorded daily and oviposition events were inferred from abrupt weight losses. We found a strong and significant relationship between the individual mobility and the time between egg pods laid (interpod period). Individual egg-laying was reduced by a rate of 0.36 eggs per day with each meter increase in mean daily activity radius. The trade-off was not biased by the size of the females, that is, constitution did not positively influence both offspring number and mobility. Egg-load had no significant influence on the individual distances travelled. We could demonstrate that mobility - as induced and selected for by foraging, thermoregulation, predator escape, shelter seeking, and reproduction - can be directly paid off by fecundity. This direct consequence of mobility on individual fitness was detected for the first time in a walking insect.

A dose-ranging study to determine the efficacy and safety of 1, 2, and 4mg of dienogest daily for endometriosis.

OBJECTIVES: To compare the efficacy and safety of dienogest at doses of 1, 2, and 4mg/day orally in the treatment of endometriosis. METHODS: An open-label, randomized, multicenter, 24-week comparative trial in women with histologically confirmed endometriosis. Efficacy was assessed by second-look laparoscopy and patient-reported symptoms. Statistical tests included chi(2) and Wilcoxon signed rank tests. RESULTS: Dienogest reduced mean revised American Fertility Society scores from 11.4 to 3.6 (n=29; P<0.001) in the 2-mg group and from 9.7 to 3.9 (n=35; P<0.001) in the 4-mg group. Dienogest at 2 and 4mg/day was associated with symptom improvements in substantial proportions of women. Both dienogest doses were generally well tolerated, with low rates of treatment discontinuation due to adverse events. The 1-mg dose arm was discontinued owing to insufficient bleeding control. CONCLUSION: Dienogest at 2mg once a day is recommended as the optimal dose in future studies of endometriosis.

Complementarity effects through dietary mixing enhance the performance of a generalist insect herbivore.

The ontogenetic niche concept predicts that resource use depends on an organism's developmental stage. This concept has been investigated primarily in animals that show differing resource use strategies as juveniles and as adults, such as amphibians. We studied resource use and performance in the grasshopper Chorthippus parallelus (Orthoptera, Acrididae) provided with food plant mixtures of either one, three or eight plant species throughout their development. C. parallelus survival and fecundity was highest in the food plant mixture with eight plant species and lowest in the treatments where only one single plant species was offered as food. C. parallelus' consumption throughout its ontogeny depended on sex, and feeding on different plant species was dependent on a grasshopper's developmental stage. To depict grasshopper foraging in food plant mixtures compared to foraging on single plant species, we introduce the term "relative forage total" (RFT) based on an approach used in biodiversity research by Loreau and Hector (Nature 413:548-274, 2001). RFT of grasshoppers in food plant mixtures was always higher than what would have been expected from foraging in monocultures. The increase in food consumption was due to an overall increase in feeding on plant species in mixtures compared to consumption of the same species offered as a single diet. Thus we argue that grasshopper foraging exhibits complementarity effects. Our results reinforce the necessity to consider development-related changes in insect herbivore feeding. Thorough information on the feeding ontogeny of insect herbivores could not only elucidate their nutritional ecology but also help to shed light on their functional role in plant communities.