Body length rather than routine metabolic rate and body condition correlates with activity and risk-taking in juvenile zebrafish Danio rerio.

In this study, the following hypotheses were explored using zebrafish Danio rerio: (1) individuals from the same cohort differ consistently in activity and risk-taking and (2) variation in activity and risk-taking is linked to individual differences in metabolic rate, body length and body condition. To examine these hypotheses, juvenile D. rerio were tested for routine metabolic rate and subsequently exposed to an open field test. Strong evidence was found for consistent among-individual differences in activity and risk-taking, which were overall negatively correlated with body length, i.e. larger D. rerio were found to be less active in a potentially dangerous open field and a similar trend was found with respect to a more direct measure of their risk-taking tendency. In contrast, routine metabolic rate and body condition were uncorrelated with both activity and risk-taking of juvenile D. rerio. These findings suggest that body length is associated with risk-related behaviours in juvenile D. rerio for which larger, rather than smaller, individuals may have a higher risk of predation, while the role for routine metabolic rate is relatively limited or non-existent, at least under the conditions of the present study.

Behaviour in a standardized assay, but not metabolic or growth rate, predicts behavioural variation in an adult aquatic top predator Esox lucius in the wild.

This study tested for links among behaviour, state and life-history variables as predicted by the pace-of-life hypothesis in adult pike Esox lucius. First, a standardized open-field behavioural assay was developed to assess individual behaviour of wild-captured adult E. lucius. Behaviour within the standardized assay predicted swimming behaviour in the lake, providing an ecological validation of the assay. There was no relationship between standardized behaviour and any of the life-history and state variables, including metabolism, body condition, juvenile growth rate and adult growth rate in contrast to predictions from the pace-of-life hypothesis. This study demonstrates that it is possible to assess ecologically relevant behavioural variation in a large-bodied top predator using a standard open-field assay, but it is noteworthy that this standardized behaviour is not systematically related to standard metabolism or growth.

Fish and robot dancing together: bluefin killifish females respond differently to the courtship of a robot with varying color morphs.

The experimental integration of bioinspired robots in groups of social animals has become a valuable tool to understand the basis of social behavior and uncover the fundamental determinants of animal communication. In this study, we measured the preference of fertile female bluefin killifish (Lucania goodei) for robotic replicas whose aspect ratio, body size, motion pattern, and color morph were inspired by adult male killifish. The motion of the fish replica was controlled via a robotic platform, which simulated the typical courtship behavior observed in killifish males. The positional preferences of females were measured for three different color morphs (red, yellow, and blue). While variation in preference was high among females, females tend to spend more time in the vicinity of the yellow painted robot replicas. This preference may have emerged because the yellow robot replicas were very bright, particularly in the longer wavelengths (550­700 nm) compared to the red and blue replicas. These findings are in agreement with previous observations in mosquitofish and zebrafish on fish preference for artificially enhanced yellow pigmentation.

Zebrafish response to robotic fish: preference experiments on isolated individuals and small shoals.

Recently developed bioinspired robots imitate their live counterparts in both aspect and functionality. Nevertheless, whether these devices can be integrated within the ecological niche inspiring their design is seldom tested experimentally. An elemental research question concerns the feasibility of modulating spontaneous behaviour of animal systems through bioinspired robotics. The following study explores the possibility of engineering a robotic fish capable of influencing the behaviour of live zebrafish (Danio rerio) in a dichotomous preference test. While we observe that the preference for the robotic fish never exceeds the preference for a conspecific, our data show that the robot is successful in attracting both isolated individuals and small shoals and that such capability is influenced by its bioinspired features. In particular, we find that the robot's undulations enhance its degree of attractiveness, despite the noise inherent in the actuation system. This is the first experimental evidence that live zebrafish behaviour can be influenced by engineered robots. Such robotic platforms may constitute a valuable tool to investigate the bases of social behaviour and uncover the fundamental determinants of animal functions and dysfunctions.

Epidoxorubicin versus no treatment as consolidation therapy in advanced ovarian cancer: results from a phase II study.

To compare the effect of epidoxorubicin given for 4 months versus no treatment in the survival of patients with advanced ovarian cancer and complete pathologic response after first-line surgery and chemotherapy with platinum-based schedules, we conducted a multicenter randomized clinical trial. Patients with histologic diagnosis of epithelial ovarian cancer FIGO stage III or IV at first diagnosis; complete pathologic response at second-look laparotomy/laparoscopy or complete clinic response; and those who have had first-line therapy including surgery and one regimen containing cisplatin or carboplatinum were eligible for the study and were randomly allocated to epidoxorubicin 120 mg/sqm or no treatment. A total of 64 women were allocated to epidoxorubicin and 74 to no treatment. There were 20 and 19 deaths, respectively, in the epidoxorubicin and no-treatment groups. The 3-year percent overall survival was 79.0% and 78.7%, respectively, in the no-treatment and epidoxorubicin groups (log-rank test, P= 0.93).

Risk factors for endometrial hyperplasia: results from a case-control study.

We analyzed epidemiologic characteristics of women at risk for endometrial hyperplasia (EH), using data from a case-control study. One hundred twenty nine women aged 35-73 (median 51 years) with histologically confirmed complex endometrial hyperplasia without atypies identified at the University of Milan during the period 1990-99 were examined. Controls were 258 non hysterectomized women aged 36-74 (median 52 years), admitted to a network of hospitals covering the same area where cases had been identified for conditions other than gynecological, malignant, or hormone-related. Cases with EH were more educated than controls (OR > 12 years of education vs. < 7: 2.8, 95% CI 1.7-4.8), more frequently obese (OR 2.7, 95% CI 1.5-5.0) and diabetic (OR 2.4, 95% CI 0.8-6.9). Parous women (OR 1.8) and women reporting induced abortions (OR 1.6) showed an increased risk of EH, but the associations were not statistically significant. Compared to premenopausal women, the OR of EH was 0.2 (95% 0.1-0.5) for postmenopausal ones. Compared to women reporting menopause at age 50 or less, the OR of endometrial hyperplasia was 1.5 (95% CI 0.6-3.5) and 2.2 (95%CI 0.7-6.7), respectively, in women with menopause at age 50-52 and > or = 53. Considering postmenopausal women only the OR was 3.1 (95% CI 1.1-9.3) for use of hormonal replacement therapy (HRT). We conclude that this study indicates that high education, obesity, diabetes, and HRT use increase the risk of endometrial hyperplasia.

A phase I/II study of topotecan in combination with carboplatin in recurrent epithelial ovarian cancer.

OBJECTIVE: The purpose of this study was to define the maximum tolerated dose (MTD) of topotecan given as escalating doses combined to a fixed dosage of carboplatin in late relapsing ovarian carcinomas. METHODS: Women with relapsing ovarian cancer more than 6 months after first-line treatment were eligible for the study. In the first phase of the trial, patients were allocated to escalating topotecan doses with a carboplatin fixed dose (AUC 5, according to Cockcroft's formula). If no "severe" adverse event occurred in 1 or more of the patients, the topotecan dose was increased. The starting dose of topotecan was 0.50 mg/m(2)/day, for 3 consecutive days, and the dose step was of 0.25 mg/m(2)/day, till 1.5 mg/m(2)/day. The study progressed then in a phase II trial. RESULTS: A total of 39 patients entered the trial. Twenty took part in the escalating topotecan dose phase (4 per dose level, 0.50, 0.75, 1, 1.25, and 1.50 mg/m(2)/day) and 19 in the phase II. No severe adverse event was observed in the phase I of the trial, so the MTD was not reached. In the phase II trial topotecan was given to 1 mg/m(2)/day. Overall grade 3-4 neutropenia, lasting 7 days or less, was observed in 58.9% (23 patients). Thrombocytopenia occurred in 30.8% (12 patients) and grade 3 anemia in 25.6% (10 patients) of subjects. No life-threatening event occurred. Platelets or red blood cell transfusions were given in three cases (7.8%). CONCLUSIONS: This daily-times-3-day schedule of topotecan in combination with carboplatin is safe.

A phase I-II trial of high-dose ifosfamide in patients with ovarian cancer refractory or resistant to platinum and/or paclitaxel-containing chemotherapy.

AIMS AND BACKGROUND: To evaluate the toxicity of high-dose ifosfamide in ovarian cancer patients refractory or resistant to platinum and/or paclitaxel-containing chemotherapy. METHODS: This was an open, non-randomized phase I-II trial of high-dose ifosfamide. Eligibility criteria were: patients aged 18-75 years affected by ovarian cancer with refractory or resistant disease or early relapse after first-line treatment including platinum or paclitaxel. Three patients were given escalating ifosfamide doses; if no severe adverse events occurred, the ifosfamide dose was increased. The starting dose of ifosfamide was 10 g/m2 i.v. and the dose increase was 1 g/m2 every four weeks for a total of five courses; 12 g/m2 was the maximum ifosfamide dose to be administered. The trial then progressed to a phase II trial, in which ifosfamide was given at the maximum tolerated dose reached during the escalating dose phase. RESULTS: A total of 36 patients entered the trial. Nine patients were involved in phase I of the study; 3 received 10 g/m2 ifosfamide, 3 11 g/m2 and 3 12 g/m2. Of the 32 evaluable patients 6 (18.8%) achieved a complete response and three (9.4%) a partial response, giving an overall response rate of 28.1% (95% CI, 15-61% based on Poisson's approximation). The median number of ifosfamide courses was five. G1, G2 and G3 neurotoxicity was reported in 3 (8%), 2 (5%) and 2 (5%) patients, respectively. CONCLUSION: This phase I-II trial indicates that high-dose ifosfamide has some activity but also a relevant degree of toxicity in resistant or refractory platinum and paclitaxel-pretreated ovarian cancer.

Pelvic and paraortic lymph nodal status in advanced ovarian cancer and survival.

BACKGROUND: In order to analyze the prognostic role of node involvement in advanced ovarian cancer, we have analyzed data from a randomized clinical trial on advanced ovarian cancer. METHODS: Cases were 456 women who entered a randomized multicentric clinical trial comparing two cisplatin-based schemes of treatment after cytoreductive surgery for advanced stage III-IV ovarian cancer. They underwent selective pelvic and/or paraortic lymphadenectomy. RESULTS: A total of 161 (35.3%) cases had positive nodes. The frequency of positive nodes was statistically significantly higher in FIGO stage IV than in stage III. Also grade 3 tumors were more likely to have positive nodes than grade 1-2 tumors. No association was observed between nodal status and response to chemotherapy. The 3-year survival was 46.2 (standard error (SE) = 3.4 based on 147 deaths) and 44.6 (SE = 4.4, based on 84 deaths), respectively, in negative and positive node groups. The corresponding values, when the analysis was performed considering only subjects with residual tumor <1 cm or absent, after first-line cytoreductive surgery were 66.2 (SE = 5.7) and 62.4 (SE = 9.6). CONCLUSIONS: We did not find any association between nodal status and survival. Particularly, nodal status was not a prognostic factor for survival in the subgroup of women with residual tumor <1 cm or absent after cytoreductive surgery.